Материал: MasterPass _ Pharmacology in 7 Days for Medical Students

PHARMACOLOGY IN 7 DAYS FOR MEDICAL STUDENTS

endogenous release of ACTH, in turn suppressing the synthesis of abnormal forms of glucocorticoids.

cDifferential diagnosis of Cushing’s syndrome.

2 Non-adrenal disorders:

a Many inflammatory/immunologic disorders, e.g. asthma, connective tissue disorders (like SLE, rheumatoid arthritis, etc.), exophthalmos and organ transplantation. b Malignancies: Hematopoietic cancers and chemotherapy-induced vomiting.

cNeurologic disorders: Multiple sclerosis.

dPregnancy: Betamethasone is given to pregnant women in preterm labour. The aim is to hasten lung maturity of the preterm fetus. If not given, preterm

neonate can die because of hypoxia. e Gram-negative bacteremia.

f Raised ICP.

Glucocorticoids: side effects

1Iatrogenic Cushing’s syndrome and suppression of patients own capacity to synthesise glucocorticoids via a negative feedback effect on pituitary ACTH release.

2Secondary diabetes mellitus due to hyperglycemia and increased glycogen storage.

3Secondary hypertension due to increased mineralocorticoid activity (Na+ and water retention).

4Increased protein breakdown leading to muscle wasting.

5Increased lipolysis and characteristic redistribution of fat leading to moon face and buffalo hump (at the back of the neck).

6Osteoporosis due to increased activity of osteoclasts.

7Skin: Acne, facial plethora, hirsutism, abdominal striae (purple-coloured).

8Proximal myopathy.

9Suppression of growth in children.

10Suppression of inflammatory/immunological responses and T- and B-cell functions leading to delayed wound healing and spread of infections.

11Peptic ulceration.

12Ocular: Cataract and glaucoma.

13Menstrual disturbances.

14Precipitation of psychotic episodes like euphoria and depression.

CUSHINGS BAD MD:

Cataracts

Up all night (sleep disturbances)

Suppression of HPA axis

Hypertension/buffalo Hump

Infections

Necrosis (avascular)

Gain weight

Striae

Bone loss (osteoporosis)

Acne

Diabetes

Myopathy, moon faces

Depression and emotional changes

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THERAPEUTIC USES AND SIDE EFFECTS

Aspirin: therapeutic uses

1 Three therapeutic dose ranges:

a <300 mg/day: in this dose range aspirin is used as an antiplatelet agent.

b300–2400 mg/day: in this dose range aspirin is used as an antipyretic agent and analgesic.

c 2400–4000 mg/day: in this dose range aspirin is used as an anti-inflammatory and uricosuric agent.

2In neonates: Patent Ductus Arteriosus (PDA) closure after birth.

3In females: to treat dysmenorrhea.

4Prevention of familial polyposis coli (FPC)/CA colon.

5Bartter’s syndrome.

6Niacin-induced cutaneous flushing (by inhibiting PGD2).

7Systemic mastocytosis.

Aspirin: side effects

1GIT: Commonest side effect = peptic ulceration (gastric/duodenal). Complications of peptic ulcers include upper GI haemorrhage, perforation (→ peritonitis) and gastric-outlet obstruction (due to excessive fibrosis). Aspirin-induced hypoprothrombinemia can also cause bleeding.

2Kidneys: are often affected, by regular administration of aspirin. Important effects on kidneys include acute renal failure and interstitial nephritis.

3Lungs: Aspirin can precipitate an acute attack of bronchial asthma in patients who are hypersensitive to this drug (especially those who are concomitantly suffering

from nasal polyps). The mechanism is decreased synthesis of PGs and increased synthesis of leukotrienes (→ bronchoconstriction).

4Toxicity: Salicylism:

•If taken in large doses, aspirin can cause tinnitus, deafness, vertigo, hyperventilation and respiratory acidosis.

•At still higher doses, aspirin can cause metabolic acidosis, hyperpyrexia, dehydration, CV collapse, coma, convulsions and death.

5Reye’s syndrome in children: If aspirin is given to children with viral infections, they can develop Reye’s syndrome (hepatic fatty degeneration → encephalopathy).

6Premature closure of PDA.

7Prolongation of labour.

ASPIRIN: Asthma Salicylism

Peptic ulcer disease/Phosphorylation-oxidation uncoupling/PPH/Platelet disaggregation/Premature closure of PDA

Intestinal blood loss Reye’s syndrome Idiosyncracy

Noise (tinnitus)

Colchicine: therapeutic uses

1Treatment of an acute attack of Gout arthritis.

2Colchicine (in low doses) is used to prevent recurrent attacks of Gouty arthritis.

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PHARMACOLOGY IN 7 DAYS FOR MEDICAL STUDENTS

3Prevention of attacks of acute Mediterranean fever.

4Psoriasis.

5Primary biliary cirrhosis.

6Sarcoid arthritis.

Colchicine: side effects

1Colchicine can severely damage liver and kidneys; overdosage (often fatal) must therefore be avoided.

2NVD, abdominal pain, burning throat and haemorrhagic gastroenteritis (on oral administration).

3Bone marrow suppression.

4Peripheral neuritis and ascending CNS depression.

5Myopathy and muscular paralysis.

6Azoospermia.

7Nephrotoxicity and extensive vascular damage.

8Hair loss.

Morphine: therapeutic uses

1Relief of severe pain: It also relieves the emotional and sensory aspects of pain. It can be given orally, parenterally (I/V/I/M) and via epidural and transdermal route.

2Relief of anxiety.

3Left ventricular failure (LVF), with massive pulmonary oedema.

4Pre-anaesthetic and intra-operative medication.

5Terminal care of cancer patients.

6Antitussive (cough reflex suppressed by an unknown mechanism).

7Antidiarrhoeal (opioid receptors in the enteric nervous system stimulated → ↓ intestinal peristalsis). Constipation is a commonly known side effect of opioids.

Morphine: side effects

SCRAM:

Synergistic CNS depression with other drugs

Constipation

Respiratory depression

Addiction

Miosis

Morphine: pharmacological effects

MORPHINES:

Miosis

Orthostatic hypotension and bradycardia

Respiratory depression

Pain suppression

Histamine release/Hormonal alterations

Increased smooth muscle activity (biliary tract constriction)

Nausea

Euphoria

Sedation

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THERAPEUTIC USES AND SIDE EFFECTS

Morphine: effects at mu receptor

PEAR:

Physical dependence

Euphoria

Analgesia

Respiratory depression

Naloxone: therapeutic uses

1Antidote for acute opioid poisoning. There are multiple causes of coma with respiratory depression; opioid poisoning being one of them. If respiratory depression is d/t opioid poisoning, Nalaxone administration will rapidly reverse it thus differentiating coma with respiratory depression d/t opioid poisoning from other causes.

2To diagnose a case of opioid addict.

3Shock.

The Narcotic Antagonists are NAloxone and NAltrexone.

Local anaesthetics: therapeutic uses

1Surface anaesthesia (drops and sprays for eye, ear and laryngeal anaesthesia).

2Infiltration anaesthesia.

3Spinal anaesthesia (into the subarachnoid space).

4Epidural anaesthesia (for painless child birth).

5Nerve blocks (e.g. brachial plexus block).

6As an analgesics (in malignancy).

7As an anti-arrhythmic (lignocaine I/V for ventricular tachycardia).

Local anaesthetics: side effects

1CNS: All local anaesthetists are capable of producing CNS side effects, most importantly, tonic-clonic convulsions, respiratory and cardiovascular depression and coma. These side effects are treated with diazepam or a short acting barbiturate such as thiopental; additionally, oxygen is given to prevent hypoxia. Occasionally, in non-responding cases, a neuromuscular blocking agent can be used to alleviate convulsions.

2CVS:

aWith the exception of cocaine (a vasoconstrictor), all local anaesthetists are vasodilators. Thus they can cause hypotension, especially when given intravenously.

bCocaine, being a vasoconstrictor, can produce MI (due to coronary vasoconstriction), hypertension (due to systemic vasoconstriction) and cerebral haemorrhage.

cLocal anaesthetists can also produce heart blocks and other arrhythmias. Local anaesthetist, most notorious for its cardiovascular toxicity, is bupivacaine. When given intravenously, it can cause both hypotension and cardiac arrhythmias. It is difficult to treat cardiovascular toxicity of bupivacaine.

3Local neurotoxic effect: Local anaesthetists when injected locally may cause permanent damage to the nerves of that area.

4Side effects caused by metabolites: Metabolites of prilocaine are known to cause methemoglobinemia.

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5Allergic manifestations: include allergic dermatitis, asthmatic attack or severe fatal anaphylactic reaction.

Lignocaine: therapeutic uses

1MI.

2Digitalis intoxication.

3Ventricular tachycardia.

4As a local anaesthetic.

5Open heart surgery.

Sedatives/hypnotics/benzodiazepines/barbiturates: therapeutic uses

1Relief of anxiety: Buspirone produces anxiolytic effect without inducing sedation. It takes 1 week to produce full therapeutic effect. It is most commonly used to treat generalised anxiety in patients with a history of substance abuse.

2Relief of panic and phobic disorders: Alprazolam and clonazepam are more efficacious than other benzodiazepines in treating panic and phobic disorders (neophobia/ agoraphobia).

3Insomnia: To induce and maintain sleep.

4Pre-anaesthetic medication, induction and maintenance of anaesthesia: Thiopental is commonly used for the induction of anaesthesia. Benzodiazepines (like diazepam and midazolam) are used for sedation and amnesia before medical/ surgical procedures.

5Epilepsy: Phenobarbitone is often used as an anti-epileptic.

6Muscle spasm: Diazepam is often used as a muscle relaxant.

7Ethanol and sedative/hypnotic withdrawal states: Long-acting drugs like diazepam and chlordiazepoxide are used in these states.

8Psychiatric disorders (like depression for short periods of time).

Benzodiazepines: antidote

‘Benish is off with the flu’:

Benzodiazepine effects off with Flumazenil.

Benzodiazepines: pharmacological actions

‘Ben SCAMs Sara into seduction not by brain but by muscle’: Sedation

antiConvulsant anti-Anxiety Muscle relaxant

Not by brain: No antipsychotic activity.

Benzodiazepines: ones not metabolised by the liver (safe to use in liver failure)

‘Outside The Liver’: Oxazepam Temazepam Lorazepam

These undergo extrahepatic metabolism and do not form active metabolites.

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