NEET MDS Lessons
Pharmacology
Beta-Adrenergic blocking Agents
• Prototype - Propranolol
• Prevent or inhibit sympathetic stimulation
– Reduces heart rate
– Myocardial contractility
– Reduce BP - decreases myocardial workload and O2 demand
• In long-term management used to decrease frequency and severity of anginal attacks
• Added when nitrates do not prevent anginal episodes
• Prevents exercise induced tachycardia
• Onset of action 30 min after oral dose. 1-2 min IV
Therapeutic Actions
• Block Beta adrenergic receptors in the heart and juxtaglomerular apparatus
• Decrease the influence of the sympathetic nervous system decreasing excitability of the heart
• Decrease cardiac output.
• Indicated for long term management of anginal pectoris caused by atherosclerosis
Atenolol, metoprolol, and nadolol have the same actions, uses, and adverse effects as propranolol, but they have long half-lives and can be given once daily. They are excreted by the kidneys, and dosage must be reduced in clients with renal impairment.
Mefenamic acid
Analgesic, anti‐inflammatory properties less effective than aspirin
Short half‐lives, should not be used for longer than one week and never in pregnancy and in children.
Enhances oral anticoagulants
Used to treat pain, including menstrual pain. It decreases inflammation (swelling) and uterine contractions.
Carbamazepine (Tegretol): most common; for generalized tonic-clonic and all partial seizures; especially active in temporal lobe epilepsies
Mechanism: ↓ reactivation of Na channels (↑ refractory period, blocks high frequency cell firing, ↓ seizure spread)
Side effects: induces hepatic microsomal enzymes (can enhance metabolism of other drugs)
TRICYCLIC ANTIDEPRESSANTS
e.g. amitriptyline, imipramine, nortriptyline
Belong to first generation antidepressants
ACTION:
Inhibit 5-HT(5-hydroxytryptamine) and norepinephrine reuptake
slow clearance of norepinephrine & 5-HT from the synapse
enhance norepinephrine & 5-HT neuro-transmission
MODE OF ACTIONMODE OF ACTION
TCAs also block
– muscarinic acetylcholine receptors
– histamine receptors
– 5-HT receptors
– α1 adrenoceptors
Onset of antidepressant activity takes 2-3 weeks
PHARMACOKINETICS
- Readily absorbed from the gastro-intestinal tract
- Bind strongly to plasma albumin
- Has a large volume of distribution(as a result of binding to extravascular tissues)
- Undergo liver CYP metabolism into biologically active metabolites
- These metabolites are inactivated via glucuronidation and excreted in urine
ADVERSE DRUG REACTIONS
Antimuscarinic - dry mouth, blurred vision, constipation and urinary retention
Antihistamine – drowsiness
adrenoceptor blockage(+/- central effect) postural hypotension
Reduce seizure threshold
Testicular enlargement, gynaecomastia, galactorrhoea
AV-conduction blocks and cardiac arrhythmias
TOXICITY
- Fatal in toxicity
- Most important toxic effect is, slowing of depolarisation of the cardiac action potential by blocking fast sodium channels ("quinidine-like" effect)
- delays propagation of depolarisation through both myocardium and conducting tissue
- prolongation of the QRS complex and the PR/QT intervals
- predisposition to cardiac arrhythmias
DRUG INTERACTIONS
Pharmacodynamic:
– ↑ sedation with antihistamines, alcohol
– ↑ antimuscarinic effects with anticholinergics– ↑ antimuscarinic effects with anticholinergics
– Hypertension and arrhythmias with MAOIs- should be given at least 14 days apart
Pharmacokinetic (via altering CYP metabolism)
– ↓ plasma concentration of TCA by- carbamazepine, rifampicin
– ↑ plasma concentration of TCA by- cimetidine, calcium channel blockers,fluoxetine
OTHER CLINICAL USES OF AMITRIPTYLINE
- Treatment of nocturnal enuresis in children
- Treatment of neuropathic pain
- Migraine prophylaxis
Beta - Adrenergic Blocking Agents
Mechanisms of Action
- Initial decrease in cardiac output, followed by reduction in peripheral vascular resistance.
- Other actions include decrease plasma renin activity, resetting of baroreceptors, release of vasodilator prostaglandins, and blockade of prejunctional beta-receptors.
Advantages
- Documented reduction in cardiovascular morbidity and mortality.
- Cardioprotection: primary and secondary prevention against coronary artery events (i.e. ischemia, infarction, arrhythmias, death).
- Relatively not expensive.
Considerations
- Beta blockers are used with caution in patients with bronchospasm.
- Contraindicated in more than grade I AV, heart block.
- Do not discontinue abruptly.
Side Effects
- Bronchospasm and obstructive airway disease.
- Bradycardia
- Metabolic effects (raise triglyerides levels and decrease HDL cholesterol; may worsen insulin sensitivity and cause glucose intolerance). Increased incidence of diabetes mellitus.
- Coldness of extremities.
- Fatigue.
- Mask symptoms of hypoglycemia.
- Impotence.
Indications
- First line treatment for hypertension as an alternative to diuretics.
- Hypertension associated with coronary artery disease.
- Hyperkinetic circulation and high cardiac output hypertension (e.g., young hypertensives).
- Hypertension associated with supraventricular tachycardia, migraine, essential tremors, or hypertrophic cardiomyopathy.
Beta adrenergic blocker Drugs
Atenolol 25-100
Metoprolol 50-200
Bisoprolol 2.5-10
Pramlintide -Amylin mimetics
Mechanism
synthetic analogue of human amylin that acts in conjunction with insulin
↓ release of glucagon
delays gastric emptying
Clinical use
type I and II DM
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