Материал: MasterPass _ Pharmacology in 7 Days for Medical Students

THERAPEUTIC USES AND SIDE EFFECTS

2CVS:

•Because of negative inotropic and chronotropic effects, β-blockers can cause bradycardia, AV block and CCF.

3Respiratory system:

•By causing bronchoconstriction, β-blockers can precipitate an acute attack of asthma/COPD.

4Metabolic:

•In case a diabetic develops hypoglycemia, the symptoms of hypoglycemia will be masked by β-blockers. Hypoglycemia induces sympathomimetic symptoms (like anxiety, tremors, palpitations, etc.), which will be masked by β-blockers.

Thus hypoglycemia may go unnoticed. β-blockers also decrease glucose mobilisation from the liver leading to further worsening of hypoglycemia.

Untreated hypoglycemia can cause permanent brain damage. Because of this reason β-blockers are relatively contraindicated in diabetes mellitus.

5Sexual disturbances:

•Erectile dysfunction in males.

6Peripheries:

•Coolness and fatigue of extremities d/t decreased blood flow to skeletal muscles.

7Oculo-mucocutaneous syndrome:

•Characterised by skin rash (psoriasis), dryness of conjunctiva, corneal ulcers and ulceration of nasal mucosa.

Beta-blockers: side effects

‘BBC Lost Viewership In Rawalpindi’: Bradycardia

Bronchoconstriction Claudication

Lipids

Vivid dreams and nightmares –ve Inotropic action

Reduced sensitivity to hypoglycemia

Beta-blockers: main contraindications, cautions

ABCDE:

Asthma

Block (heart block)

COPD

Diabetes mellitus

Electrolyte (hyperkalemia)

Alpha adrenergic blockers: therapeutic uses

Non-selective alpha-antagonists

1 Hypertension:

a Essential hypertension.

b Many drugs of abuse (e.g. amphetamine, cocaine, etc.) can cause severe hypertension. Alpha-antagonists by causing vasodilatation can effectively treat this drug-induced hypertension.

c Sudden cessation of clonidine can cause rebound hypertension. This

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PHARMACOLOGY IN 7 DAYS FOR MEDICAL STUDENTS

phenomenon can be treated with phentolamine.

2Pheochromocytoma: Phenoxybenzamine is the drug of choice.

3Carcinoid syndrome (secretes serotonin): Phenoxybenzamine blocks serotonin receptors.

4Mastocytosis: Phenoxybenzamine blocks H1 receptors.

5Accidental local infiltration of a potent α-agonist (e.g. epinephrine) can cause tissue necrosis d/t vasoconstriction. Alpha-antagonists can reverse this action.

6Erectile dysfunction: Phentolamine or yohimbine injection directly into the penis.

Selective alpha-antagonists (prazosin; doxazosin; terazosin)

1Hypertension.

2BPH.

Alpha adrenergic blockers: side effects

1Postural/orthostatic hypotension, especially with the first dose. Therefore first dose is usually small and taken just before going to the bed.

2Reflex tachycardia: In patients with coronary artery disease, angina may be precipitated due to reflex tachycardia. Tachycardia is less severe with α1-selective blockers.

3N, V, D due to parasympathetic dominance over the sympathetic discharge.

4Nasal stuffiness.

5Sedation.

6Failure/delayed/retrograde ejaculation.

Methyldopa: therapeutic uses

1 Hypertension:

aEssential HTN: The major compensatory response is Na+ and water retention. The added advantage of methyldopa (as an antihypertensive agent) is that it

can be used in late pregnancy as it does not produce toxic effects on mother and fetus.

b Hypertensive crisis: 200–250 mg I/V; can be repeated after 6hrs.

cSudden discontinuation of methyldopa or clonidine should be avoided otherwise severe rebound hypertension can occur, which can either be treated by reinstituting methyldopa/clonidine therapy or by administering alphaantagonists, e.g. phentolamine.

2Carcinoid syndrome: is d/t carcinoid tumour of enterochromaffin cells in the intestine producing large amounts of serotonin, substance P, PGs and bradykinin. Serotonin causes increased GI motility with resultant diarrhoea. Methyldopa reduces serotonin formation.

Clonidine: therapeutic uses

1HTN.

2Alcohol/drug withdrawal.

Guanithidine: therapeutic uses

1Used to treat moderate to severe hypertensive cases.

2Autonomic hyperreflexia.

3Ophthalmic uses: Glaucoma; Graves’ disease (lid retraction and thyrotoxicosis).

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THERAPEUTIC USES AND SIDE EFFECTS

Dantrolene: therapeutic uses

1Muscle spasms: Certain CNS diseases (e.g. cerebral palsy, multiple sclerosis and stroke) are associated with abnormally high reflex activity in those neuronal pathways that control skeletal muscles. The result is painful muscle spasms. Dantrolene by reducing the release of calcium from the sarcoplasmic reticulum relieves such spasms.

2Malignant hyperthermia: General anaesthetic agents (like succinylcholine and tubocurarine) can cause massive release of calcium from the sarcoplasmic reticulum of the skeletal muscles. Dantrolene, by reducing the release of calcium from the sarcoplasmic reticulum, is the drug of choice in this condition.

Adrenaline: therapeutic uses

1Emergency uses:

•Acute anaphylactic shock.

•Cardiac resuscitation.

2Topical uses:

•Topical hemostasis.

•Topical agent for glaucoma: Alpha agonists by inducing mydriasis reduce conjunctival itching.

3Use in anaesthesia:

•To prolong the actions of infiltration anaesthesia.

Adrenaline: side effects

1It can produce anxiety-related symptoms, e.g. fears, restlessness, headache, tremors and palpitations.

2Cardiac arrhythmias: Excessive sympathomimetic effect can precipitate arrhythmias.

3Coronary vasoconstriction: It can precipitate angina pectoris or myocardial infarction.

4Tissue necrosis (d/t intense vasoconstriction).

5Pulmonary oedema/haemorrhage.

6Cerebral haemorrhage.

Noradrenaline: therapeutic uses

1Cardiogenic shock.

2Oliguric patients.

Isoprenaline: therapeutic uses

1Used as a bronchodilator.

2Cardiac stimulant in heart blocks.

3For maintenance of systolic BP in cardiogenic and septic shock.

Salbutamol: therapeutic uses

1Bronchial asthma.

2COPD.

3To prevent premature labour (Ritodrine is preferred).

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Alpha-1 agonists: therapeutic uses

1Nose: As nasal decongestant.

2Eyes: Alpha agonists (e.g. phenylephrine) by inducing mydriasis, reduce conjunctival itching. These drugs do not cause cycloplegia. Newer α2-selective agonists (e.g. Apra-clonidine) reduce aqueous synthesis and are thus useful in the treatment of glaucoma.

3Hypotension:

aFor treating spinal shock (α agonists → vasoconstriction → ↑ BP). Conversely, shock due to septicemia or MI is made worse by α agonists and thus they should be avoided in such cases.

bChronic orthostatic hypotension d/t inadequate sympathetic tone: Ephedrine or a new α1-agonist midodrine can be used.

Ephedrine: therapeutic uses

1Nasal decongestant (causes constriction of nasal blood vessels). Nowadays alpha-1 selective agonists are used (like xylometazoline).

2As mydriatics.

3As presser agent in chronic orthostatic hypotension.

4Urinary stress incontinence, especially in females because it contracts the detrusor muscle and relaxes the sphincter.

5Bronchial asthma (causes bronchodilatation; given prophylactically). Beta-2 selective agonists are preferred nowadays.

6Whooping cough (relieves the paroxysms).

7Myasthenia gravis (stimulates NM transmission). It thus enhances the effect of neostigmine (an anticholinesterase).

8In skin allergies (counteract the effects of histamine by causing vasoconstriction).

Ergot alkaloids: therapeutic uses

1 Migraine:

a Acute attack: Ergotamine is used.

b Prevention: Ergonovine and methysergide are used.

2 Postpartum haemorrhage: Ergotamine and ergonovine are used.

Migraine: prophylaxis drugs

‘Very Volatile Pharmacotherapeutic Agents For Migraine Prophylaxis’: Verapamil

Valproic acid Pizotifen Amitriptyline Flunarizine Methysergide Propranolol

Digitalis: therapeutic uses

1CCF: Digitalis → positive inotropic effect → ↑ force of cardiac contraction.

2Arrhythmias:

aAtrial fibrillation/flutter, associated with hypotension or pulmonary oedema. Digitalis decreases the ventricular rate by depressing SA node, decreasing the

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AV nodal conduction (negative chronotropic effect) and improving cardiac contraction (positive inotropic effect).

b Paroxysmal atrial tachycardia. c AV-nodal tachycardia.

Calcium channel blockers: therapeutic uses

1 CVS:

a HTN. b Angina.

cSupraventricular arrhythmias: Verapamil and diltiazem are used; nifedipine and other dihydropyridines are not used as anti-arrhythmics (nifedipine →

↓ B.P → reflex tachycardia → facilitates arrhythmias rather than suppressing them).

2 CNS:

a Subarachnoid haemorrhage (SAH): Nimodipine is used. b Migraine prophylaxis.

3Raynaud’s syndrome.

4Preterm labour.

Ace inhibitors: therapeutic uses

1CVS:

•HTN (usually given with thiazide diuretics; can be given with β-blockers).

•MI.

•CCF.

2Diabetic Nephropathy.

Captopril (an ACE inhibitor): side effects

CAPTOPRIL:

Cough Angioedema/Agranulocytosis Proteinuria/Potassium excess Taste changes

Orthostatic hypotension

Pregnancy contraindication/Pancreatitis/Pressure drop (first dose hypertension) Renal failure (and renal artery stenosis contraindication)/Rash

Indomethacin inhibition Leukopenia/Liver toxicity

Vasodilator drugs (hydralazine; minoxidil; Na nitroprusside): therapeutic uses

1 Hypertensive emergency.

Nitroglycerin: therapeutic uses

1For prophylaxis and treatment of classical angina pectoris.

2Treatment of variant/prinzmetal’s (angiospastic) angina.

3Treatment of unstable angina.

4Cyanide poisoning.

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