pharmacology journal

PHARMACOLOGY JOURNAL

Allergy And Anaphylaxis

Analgesics

Anaesthetic Agents

Anti-Infectives

Cardiovascular Drugs

Blood And Electrolytes

Dermatological Drugs

Ear, Nose and Throat Drugs

Endocrine Drugs

Eye Drugs

Gastrointestinal Drugs

Genitourinary Drugs

Immunomodulators and Antineoplastics

Musculoskeletal Drugs

Neurological Drugs

Obstetric and Gynaecological Drugs

Psychotropic Drugs

Respiratory Drugs

1. Acyclovir

2. Adenosine

3. Adrenaline

4. Amiodarone

5. Amitriptyline

6. Amphetamine/MDMA

7. Aspirin/salicylates

8. Atropine

9. Azathioprine

10. Calcium chloride

11. Carbamazepine

12. Ceftriaxone

13. Charcoal

14. Chloramphenicol

15. Chloroquine

16. Chlorpromazine

17. Ciprofloxacin

18. Clonidine

19. Cocaine

20. Codeine

21. Colchicine

22. Cyclophosphamide

23. Diazepam

24. Digoxin

25. Diltiazem

26. Dobutamine

27. Dopamine

28. Enalapril

29. Ethanol

30. Fentanyl

31. Flumazenil

32. Fluoxetine

33. Frusemide

34. Gentamicin

35. Gliclizide

36. Glucagon

37. Glyceryl trinitrate

38. Haloperidol

39. Halothane

40. Heparin

41. Hydralazine

42. Ibuprofen

43. Insulin

44. Iron

45. Isoniazid

46. Ketamine

47. Levo-dopa

48. Lignocaine

49. Lithium

50. Magnesium

51. Metformin

52. Methotrexate

53. Metoclopramide

54. Metronidazole

55. Midazolam

56. Morphine

57. N-Acetylcysteine

58. Naloxone

59. Neostigmine

60. Nifedipine

61. Nitrous oxide

62. Octreotide

63. Omeprazole

64. Ondansetron

65. Oxygen

66. Oxytocin

67. Paracetamol

68. Penicillin

69. Phenobarbitone

70. Phenytoin

71. Potassium chloride

72. Prazosin

73. Prednisone

74. Promethazine

75. Propranolol

76. Propofol

77. Propylthiouracil (PTU)

78. Quinine

79. Ranitidine

80. Rifampicin

81. Salbutamol

82. Simvastatin

83. Sodium bicarbonate

84. Sotalol

85. Streptokinase

86. Sumatriptan

87. Suxamethonium

88. Tetracycline

89. Theophylline

90. Thiopentone

91. Thyroxine

92. t-PA

93. Valproic acid

94. Vancomycin

95. Vasopressin

96. Vecuronium

97. Venlafaxine

98. Verapamil

99. Warfarin

100. Zidovudine

ALLERGY AND ANAPHYLAXIS

Anaphylaxis

Most anaphylactic reactions are mediated by IgE, they ae typically precipitated by insect stings, foods, drugs, blood products, latex, food chemicals or additives

Symptoms of Anaphylaxis inc.

Urticaria

Angioedema

Respiratory distress – fatalities most often result from respiratory obstruction due to upper airway oedema (tongue and laryngeal) or bronchospasm with small airway obstruction

Vomiting

Diarrhoea

Hypotension – which may result in a stroke, MI, arrythmias or death

Rationale for Drug Use

Prevention of serious complications or death

Cardiorespiratory support

Symptom releif

Management of Anaphylaxis

Sympathomimetics – Adrenaline

IV fluids – required to expand intravascular volume and restore BP in combination with adrenaline

Bronchodilators – to help relieve bronchospasm

Glucagon – may help persistent hypotension in patients on beta-blockers

Corticosteroids – used to reduce duration of reaction and prevent relapse

Allergic Reactions

Moderate allergic reactions inc.

Seasonal and perennial rhinitis

Allergic conjunctivitis

Less severe reactions to insect bites and stings

Urticaria

Angioedema

Rationale for treatment is symptom relief

Identify allergen if possible – RAST (specific IgE), skin-prick testing

Avoid allergen

Management of Allergic Reactions - Antihistamines (H1 Antagonists)

Sedating Antihistamines

Cyproheptadine

Dexchlorpheniramine

Pheniramine

Promethazine Hydrochloride

Trimeprazine

Less-Sedating Antihistamines

Cetirizine

Desloratadine

Fexofenadine

Levocetirizine

Loratadine

Drug Name Adrenaline (Epinephrine)

Drug Class Sympathomimetics (Anaphylaxis)

Mode Of Action

Non-selective adrenergic agonist

- Positive inotrope and chronotrope (beta1 receptors)

- Vasodilator at low dose (beta2 receptors)

- Vasoconstrictor at high dose (alpha receptors)

- Bronchial smooth muscle relaxant (beta2 receptors)

- Stabilises mast cells

Indications

Severe allergic reactions inc. anaphylactic shock, life-threatening angioedema

Bronchospasm and croup

Cardiac arrest

Inotropic support in acute heart failure and cardiogenic shock, acute exacerbation of chronic heart failure, septic shock, positive end expiratory pressure ventilation

Adjunct in local anaesthesia

Precautions

**There are NO contraindications in severe life-threatening allergic reactions.

- IHD and CVD – increased sensitivity to sympathomimetic effects inc. arrhthmias, angina, myocardial ischaemia

Contraindicated in:

- Phaeochromocytoma

- Tachyarrhythmias

Adverse Effects

Common

Anxiety, fear

Headache

Palpitations

Tachycardia

Restlessness

Tremor

Dizziness

Dyspnoea

Weakness

Sweating

Pallor

Hyperglycaemia

Infrequent

Excessive increase in BP, ventricular arrhythmias, pulmonary oedema, angina, peripheral ischaemia, necrosis (at infusion site)

Rare

Allergic reaction

Overdose, or Rapid IV Administration

Arrhythmias, severe hypertension, cerebral haemorrhage, pulmonary oedema

Dosage

Adult - Anaphylaxis

IM 10micrograms/kg up to 500micrograms (EpiPen 300micrograms, 3mL)

IV 5micrograms/kg

Adult – Cardiac Arrest

IV 0.5-1mg (Adrenaline 1:10,000 is 0.1mg/mL, 10mL)

IV Infusion 1-4micrograms/minute

Drug Name Promethazine Hydrochloride

Drug Class Antihistamine

Mode Of Action

Antihistamines are divided into 2 groups: older sedating drugs and newer less sedating drugs.

Sedating antihistamines (like promethazine) antagonise the action of histamine at H1 receptors, reducing histamine-related vasodilation and increased capillary permeability. They also have anticholinergic activity, some alpha-blocking activity and some antiserotonin activity.

Less sedating antihistamines selectively anatagonise the action of histamine at H1 receptors – histamine release causes vasodilation and increases capillary permeability.

Indications

Allergic upper respiratory conditions, inc. rhinitis

Allergic skin conditions, inc. urticaria, contact dermatitis

Pruritis

Nausea and vomiting, inc. motion sickness

Sedation

Precautions

Contraindicated in:

- Closed angle glaucoma, increased intraocular pressure, bladder neck obstruction, hyperthyroidism – may be worsened by the anticholinergic effects of antihistamines

- Epilepsy – promethazine lowers the seizure threshold

Adverse Effects

Common

Sedation

Dizziness

Tinnitus

Blurred vision

Euphoria

Incoordination

Anxiety

Insomnia

Tremor

Nausea and vomiting

Constipation and diarrhoea

Epigastric discomfort

Dry mouth

Cough

Infrequent

Urinary retention, palpitations, hypotension, headache, hallucinations, psychosis, thrombophlebitis

Rare

Leucopenia, agranulocytosis, haemolytic anaemia, allergic reactions, arrhythmias, dyskinesia, paraesthesia, paralysis, hepatitis, seizures

Dosage

Adult (do NOT give SC, avoid IV because of risk of thrombophlebitis)

Allergy Oral 25-75mg once daily, or 10-25mg 2-3 times daily (Phenergan – 10mg, 25mg tab)

IM 25-50mg single dose

ANALGESICS

Analgesics are used to treat pain, which is clinically classified as:

Nociceptive Pain due to activation of normal pain fibres in response to a noxious stimulus (ie. injury, disease, inflammation); it may be somatic (involving superficial structures ie. skin, muscle) or visceral (involving deeper organs ie. liver, pancreas)

Neuropathic Pain due to injury, disease or dysfunction affecting the peripheral nervous system (ie. post-herpatic neuralgia, diabetic neuropathy) or central nervous system (ie. spinal cord injury, post-stroke)

Types of Analgesics

Non-Steroidal Anti-Inflammatory Drugs ( NSAIDs )

Non-Selective NSAIDs (COX-1 and COX-2 Inhibitors)

Aspirin

Diclofenac

Ibuprofen

Indomethacin

Ketoprofen

Ketorolac

Mefanamic Acid

Naproxen

Piroxicam

Sulindac

Tiaprofenic Acid

Selective NSAIDs (COX-2 Inhibitors)

Celecoxib

Meloxicam

Parecoxib

Other Non-Opioid Analgesics

Paracetamol

Opioid Analgesics

Buprenorphine

Dextropropoxyphene

Hydromorphine

Morphine

Pethidine

Codeine

Fentanyl

Methadone

Oxycodone

Tramadol

The choice of analgesic depends on the type of pain:

Drug Nociceptive Pain Neuropathic Pain

ParacetamolEffective (negligible anti-inflammatory effects)

Less effective

NSAIDs Effective (useful anti-inflammatory effects) Less effective

Opioids Effective May be effective

TCAs, Parenteral local anaesthetics, antiepileptics, clonidine

Rarely used May be effective

Route of Administration

Oral, IV, IM, SC, PCA, Transdermal, Inhaled (mainly for NO), Epidural, Intrathecal, Regional Nerve Blockade

Drug Name Aspirin (Acetylsalicylic Acid)

Drug Class Analgesic, Antipyretic, Anti-Inflammatory, Anti-Platelet

Mode Of Action

Non-selective NSAID, preventing the synthesis of prostaglandins by non-competitively inhibiting both forms of cyclo-oxygenase (COX), COX-1 and COX-2. It irreversibly inhibits COX-1 and modifies the enzymatic activity of COX-2.

COX is required for prostaglandin (pro-inflammatory) and thromboxane (promote clotting, vasoconstrictor) synthesis. Aspirin acts as an acetylating agent where an acetyl group is covalently attached to a serine residue in the active site of the COX enzyme. Hence the duration of effect depends on the rate of enzyme resynthesis.

Aspirin irreversibly blocks the formation of thromboxane A2 in platelets producing an inhibitory effect on platelet aggregation.

Indications

Inhibit platelet aggregation

Mild-Moderate pain

Fever

Rheumatic fever, Rheumatoid arthritis, Kawasaki’s disease

Precautions

Contraindicated in:

- Allergy to aspirin or other NSAIDs

- Haemophilia

- Heart failure, uncontrolled hypertension – may be exacerbated by sodium and fluid retention caused by aspirin-induced reduction in GFR and renal blood flow

- Peptic ulcer disease- increased risk of GI ulceration

- Renal and hepatic impairment – increased risk of bleeding

Adverse Effects

Common

Nausea

Dyspepsia

Vomiting

GI Ulceration or bleeding

Asymptomatic blood loss

Increased bleeding time

Headache

Dizziness

Rare

Skin reactions, iron-deficiency anaemia, renal impairment, oesophageal ulceration, major haemorrhage

Dosage

Adult 300-900mg every 4-6hrs when necessary (available in 300mg white tablets)

Drug Name Paracetamol (Acetaminophen)

Drug Class Analgesic; Antipyretic

Mode Of Action (Not fully determined)

Analgesic effec may be due to inhibition of prostaglandin synthesis centrally, and may be involved in ther mechanisms which peripherally block pain impulses.

Antipyretic effect probably due to reduced prodution of prostaglandins in the hypothalamus

Indications

Mild to moderate pain

Fever

Precautions

- Sodium restriction – soluble paracetamol products may contain large amounts of sodium

- Phenylketonuria – soluble paracetamol products may contain aspartame

Contraindicated in:

- Chronic liver disease – pts may be at increased risk of liver damage

(safe to use in pregnancy and breastfeeding)

Adverse Effects

Common

Increased transaminases (Hepatotoxicity, which can occur following paracetamol overdose)

Rare

Utricarial or erythematous rash, drug fever, mucosal lesions, hypersensitivity reactions, neutropenia, thrombocytopenia, pancytopenia, acute hepatitis, hypotension

Dosage

Adult

Oral 0.5-1g every 4-6hrs (max 4g daily)

Oral Controlled Release 2 tablets (665mg per tablet) every 6-8hrs swallowed whole (max 6 tablets daily)

IV Infusion 1g (100mL) every 4-6hrs (max 4g daily) – IV infusion given over 15min

Combination Doses

Paracetamol Codeine Combination (Panamax, Prodeine, Panadeine Forte) 1-2tablets (paracetamol 500mg, codeine 8, 15, 30mg) every 4-6hrs if needed (max 8 tablets daily)

Paracetamol Metoclopramide Combination (Anagraine, Metomax) 1-2 tablets (paracetamol 500mg, metoclopramide 5mg) at first signs of migraine, repeat every 4hrs if required

Drug Name Ibuprofen

Drug Class Analgesic; Antipyretic; Anti-Inflammatory; Antiplatelet (non-selective)

Mode Of Action

NSAIDs inhibit synthesis of prostaglandins by inhibiting cyclo-oxygenase (COX). COX is present in 2 forms, COX-1 and COX-2. Inhibition of COX-1 is associated with impaired gastric cytoprotection and anti-platelet effects. Inhibition of COX-2 is associated with anti-inflammatry and analgesic action. Reduction in GFR and renal blood flow is associated with both COX-1 and COX-2 inhibition

Indications

Rheumatoid arthritis, inc. juvenile RA

Osteoarthrtis

Other inflammatory arthropathies, inc. ankylosing spondyitis, psoriatic arthriti, Reiter’s Sydnrome

Pain, esp. due to inflammation and tissue injury (eg. period pain, metastatic bone pain, renal colic, headache, migraine, postoperative pain)

Fever

Precautions

Contraindicated in:

- Allergic reaction to NSAIDs

- Asthma – NSAIDs may increase risk of bronchospasm

- Coagulation Disorders – nonselective NSAIDs increase risk of bleeding (antiplatelet effect), while selective NSAIDs (and ?diclofenac) increase the risk of thrombosis

- Heart failure and hypertension – NSAIDs may ecacerbate sodium and fluid retention by reducing GFR and renal blood flow

- Active Peptic Ulcer Disease or GI Bleeding

- Renal Impairment – increased risk of NSAID-induced impairment

Adverse Effects

Common

Nausea

Dyspepsia

GI Ulceration or bleeding

Raised liver enzymes

Diarrhoea

Headache

Dizziness

Salt and fluid retention

Hypertension

Infrequent

Oesophageal ulceration, rectal irritation, heart failure, hyperkalaemia, renal impairment, confusion, bronchospasm, rash

Rare

Blood dyscrasias, interstitial nephritis, cystitis, nephrotic syndrome, acute renal failure, papillary necrosis, photosensitivity, epidermal necrolysis, hepatitis, aseptic meningitis, blurred vision, tinnitus, hypersensitivity

Dosage

Adult 200-400mg 3-4 times daily (Max 2400mg daily) (Nurofen is 200mg tablet)

Ibuprofen and Codeine Combination 1-2 tablets (ibuprofen 200mg, codeine 12.8mg) every 4 hrs if needed (max 6 tablets) (Nurofen Plus)

Drug Name Morphine

Drug Class Analgesic

Mode Of Action

Opioid analgesics mimic endogenous opioids by activating opioid receptors in the central and peripheral nervous systems to produce analgesia, respiratory depression, sedation and constipation. It predominantly acts as an agonist on -opioid receptors which are in high densities in the μamygdala, hypothalamus, thalamus, caudate nucleus, putamen. They reduce transmission of the pain impulse by acting pre- and post-synaptically in the spinal cord and by modulating the descending inhibitory pathways from the brain. Cough suppression occurs in the medullary centre of the brain.

Indications

Acute or chronic pain

Opioid adjunct during general anaesthesia

Precautions

Contraindicated in:

- Comatosed patients

- Epilepsy or a recognised risk for seizure (inc. head injury, metabolic disorders, alcohol and drug withdrawal, CNS infections) – increases risk of seizure

- Raised intracranial pressure – respiratory depression due to opioids may be poorly tlerated and may further increase intracranial pressure (avoid if possible)

- Biliary Colic – opioids may cause spasm of sphincter of Oddi

- Renal impairment – risk of accumulation of active/toxic metabolites

Adverse Effects – Adverse effects may limit achievement of adequate pain control, the options then inc. controlling symptoms, reducing opioid dose and ?adding adjuvant analgesic, switching to an alternate opioid

Common

Nausea and vomiing – may occur initially, an antiemetic may be given prophylactically

Dyspepsia

Drowsiness

Dizziness

Headache

Orthostatic hypotension

Itch

Dry mouth

Miosis

Urinary retention

Constipation – tolerance develops slowly, attention to fluid intake, diet and mobility plus regular laxative use is essential when chronic opioid treatment is started

Infrequent

Dose-related respiratory depression – judged by degree of sedation, respiratory rate reduction is late and an unreliable marker

Bronchospasm, confusion, hallucinations, delirium, agitation, mood changes, tremor, visual disturbances, urticaria, hypothermia, brady or tachycardia, hypertension, ureteric or biliary spasm, muscle rigidity, myoclonus, flushing due to histamine release

Rare

SIADH, anaphylaxis, seizure

Dosage

Adult

IV Initially 0.5-2mg repeated every 3-5min

SC/IM 7.5-12.5mg (20-39yo), 5-10mg (40-59yo), 2.5-7.5mg (60-69yo), 2.5-5mg (70-85yo), 2-3mg (>85yo) every 2 hrs as required

(Seredol (10, 20mg tab), Anamorph (30mg tab), MS Contin (5,10,15,30,60,100,200mg tab))

Drug Name Codeine


Mode Of Action

Codeine is a pro-drug, it is metabolised in vivo to the primary active compounds morphine and codeine-6-glucuronide. Because it needs to be metabolised to an active form there is a ceiling effect around 400-450mg, making it less addictive.

Opioid analgesics mimic endogenous opioids by activating opioid receptors in the central and peripheral nervous systems to produce analgesia, respiratory depression, sedation and constipation. They reduce transmission of the pain impulse by acting pre- and post-synaptically in the spinal cord and by modulating the descending inhibitory pathways from the brain. Cough suppression occurs in the medullary centre of the brain.

Indications

Mild to moderate acute or chronic pain

Cough suppression

Diarrhoea

Precautions

Contraindicated in:







Common


Dyspepsia

Drowsiness

Dizziness

Headache


Itch

Dry mouth

Miosis

Urinary retention


Infrequent



Rare


Dosage

Adult 30-60mg every 4 hours (Oral/SC/IM), max 240mg per 24hrs (Codeine phosphate - 30mg tab, 50mg/mL inj)

Drug Name Fentanyl


Mode Of Action

Opioid analgesics mimic endogenous opioids by activating opioid receptors in the central and peripheral nervous systems to produce analgesia, respiratory depression, sedation and constipation. They reduce transmission of the pain impulse by acting pre- and post-synaptically in the spinal cord and by modulating the descending inhibitory pathways from the brain. Cough suppression occurs in the medullary centre of the brain.

Indications

Acute pain

Opioid adjunct during general anaesthesia

Chronic pain (for patients intolerant of morphine) – first choice for use in cancer patients

Breakthrough pain

Precautions

Contraindicated in:

- Bradyarrhythmias may be exacerbated







Common


Dyspepsia

Drowsiness

Dizziness

Headache


Itch

Dry mouth

Miosis

Urinary retention


Infrequent



Rare


Dosage

Adult

Spontaneous Ventilation UV 50-100micrograms, then 25-50micrograms s required

Assisted Ventilation IV 50micrograms-3.5mg, then 50-200micrograms or more as required

Usually given in combination with a benzodiazepine such as midazolam

There are also transdermal patches which release fentanyl into body fats which slowly release into the blood stream over 48-72hrs

ANAESTHETICS

General Anaestheisa involves:

Preoperative assessment with or without premedication, to ensure that the process of anaesthesia is as safe as possible

Induction, to render the patient unconscious and unreactive to surgical stimuli (using IV or inhaled drugs)

Maintenance, to keep the patient anaesthetised for as long as the operation lasts (using IV and/or inhaled drugs with muscle relaxants and analgesics as necessary)

Reversal, if non-depolarising muscle relaxants are used, reversal with neostigmine (and an anticholinergic to prevent undesirable muscarinic effects, esp. bradycardia) is usually required when the operation is completed

Recovery, which begins when the anaesthetic is stopped and lasts until the patient is fully conscious, has stable cardiovascular status, is able to maintain own airway and is comfortable

IV General Anaesthetics

In appropriate doses IV general anaesthetic drugs produce rapid, reversible loss of consciousness and insensibility to surgical stimuli

Types of IV General Anaesthetis

Ketamine

Propofol

Midazolam

Thiopentone

Inhaled Anaesthetics

Their anaesthetic effect is directly proportional to the partial pressure of the drug in the brain, factors which shorten the induction time inc.

High inspired concentration

Increased alveolar ventilation

Reduced cardiac output

Low blood:gas solubility

Increased alveolar-to-capillary partial pressure difference

Potency is measured by minimum alveolar concentration (MAC) to which it is inverely related - MAC is the alveolar concentration that prevents movement in response to a skin incision in 50% of patients, it decreases as age increases

Types of Inhaled Anaesthetics

Volatile Anaesthetics (liquid at room temperature)

Desflurane

Isoflurane

Methoxyflurane

Sevoflurane

Other Inhaled Anaesthetics

Nitrous Oxide

Nuromuscular Blockers

Types of Neuromuscular Blockers

Neuromuscular blocking drugs produce skeletal (inc. respiratory) muscle relaxation which is used during general anaesthesia.

Non-Depolarising Neuromuscular Blockers

Atracurium

Cisatracurium

Mivacurium

Pancuronium

Rocuronium

Vecuronium

Depolarising Neuromuscular Blockers

Suxamethonium

Other Anaesthetic Agents

Alpha2 and Imidazoline Agonists

Clonidine

Dexmedetomide

Opioids (anaesthesia)

Alfentanil

Remifentanil

Anticholinergics (anaesthesia)

Glycopyrrolate

Drugs for Local Anaesthesia

Amethocaine (skin)

Bupivacaine

Cocaine

Levobupivacaine

Lidnocaine

Prilocaine

Procaine

Ropivacaine

Drug Name Ketamine

Drug Class Anaesthetic (General)

Mode Of Action

Antagonises NMDA receptors, also interacts with muscarinic receptors, descending monoaminergic pain pathways, voltage-sensitive calcium channels and opioid receptors in the brain and spinal cord

Is a potent analgesic at subanaesthetic concentrations. It can cause cardiovascular and respiratory stimulation at recommended doses, it maintains pharyngeal and laryngeal reflexes compared with other IV anaesthetic agents.

Indications

Induction and maintenance of anaesthesia

Pain relief

Precautions

Contraindicated in:

- Conditions which may be worsened by an increase in BP and/or heart rate, inc. poorly controlled hypertension, stroke, intracerebral haemorrhage, angina, recent MI, stenotic valvular heart disease, tachyarrhythmias, chronic heart failure – ketamine increases BP and heart rate

- Psychiatric disorders – hallucinations, irrational behaviour may occur

- Raised intracranial or intraocular pressure – may be further raised

- Addisions Disease, severe anaemia, myxoedema – hypnotic effect may be prolonged or potentiated

- Debilitated patients – more sensitive to adverse and anaesthetic effects

- IV anaesthetics may worsen symptoms of cardiovascular compromise (hypotension, hypovolaemia)

Adverse Effects

Common

Raised BP and HR

Increased muscle tone (sometimes tonic-clonic and resembling seizures)

Lacrimation

Hypersalivation

Raised intracranial pressure

Raised intraocular pressure

Emergence reactions – inc. vivid dreams, restlessness, confusion, hallucinations and irrational behaviour

Infrequent

Diplopia, nystagmus, postoperative nausea and vomiting, hypotension and bradycardia, pain on injection, erythema, morbilliform rash

Rare

Apnoea, laryngospasm, arrhythmias, anaphylaxis

Dosage

Adult

IV 1-4.5mg/kg (usually 2mg/kg over 60s provides anaesthesia within 30s lasting for 5-10min)

IM 6.5-13mg/kg (usually 10mg/kg provides anaesthesia within 3-4min lasting 12-25min)

Drug Name Propofol

Drug Class Anaesthetic (General)

Mode Of Action (uncertain)

Its main CNS depressant action is thought to be via the GABA receptor at a site different to that of barbiturates and benzodiazepines. May also shorten channel opening times at nicotinic acetylcholine receptors and sodium channels in the cerebral cortex.

Is most effective at suppressing pharyngeal and laryngeal reflexes allowing rapid control of the airway, inc. insertion of laryngeal mask and endotracheal intubation. Has some antiemetic effect, causing less post-operative nausea and vomiting when used alone.

Indications


Conscious sedation (midazolam, propofol)

Sedation during ventilation (midazolam, propofol)

Precautions

Contraindicated in:




- Severe respiratory compromise – further respiratory depression occurs

Adverse Effects

Common

Pain on injection

Bradycardia

Hypotension

Apnoea

Flushed skin or rash

Cough

Excitation at induction (involuntary movements inc. twitches, tremors, hypertonus and hiccup)

Infrequent

Arrhythmias, thrombosis, phlebitis at injection site

Rare

Anaphylactic reactions, seizure, fever, pancreatitis

Dosage

Adult (1% preparation – 10mg/mL available as 20, 50, 100mL preparations)

IV 2-2.5mg/kg (9-55yo), 1-1.5mg/kg (>55yo or debilitated)

Drug Name Midazolam

Drug Class Anaesthetic (General); Benzodiazepine

Mode Of Action

Potentiates the inhibitory effects of GABA throughout the CNS, resulting in anxiolytic, sedative, hypnotic, anterograde amnesic, muscle relaxant and antiepileptic effects

Is the least effective IV agent for induction of anaesthesia, but is anterograde amnesic effect may be useful.

Indications


Conscious sedation (midazolam, propofol)

Sedation during ventilation (midazolam, propofol)

Premedication

Status epilepticus

Precautions

Contraindicated in:




- Respiratory disease, sleep apnoea – compromised respiratory drive may result in hypoventilation and hypoxaemia

Adverse Effects

Common

Hypotension

Hiccup

Cough

Infrequent

Pain on injection, erythema, rash, bronchospasm, nasuea, vomiting, headache, confusion, restlessness

Rare

Arrhythmias, cardiorespiratory arrest, anaphylactic reactions

Dosage

Adult (1mg/mL 5mL; 5mg/mL 1, 3, 10mL preparations)

Conscious Sedation IV 2-2.5mg, give further 1mg as needed

Induction of anaesthesia IV 0.15-0.35mg/kg, rate2.5mg per 10s

Drug Name Thiopentone

Drug Class Anaesthetic (General); Barbiturate

Mode Of Action

Potentiates action of the inhibitory neurotransmitter GABA at multiple sites in the CNS resulting in sedative, hypnotic, anaesthetic and anticonvulsant effects. It also depressesthe actions of excitatory neurotransmitters in the CNS. Redistribution of cerebral blood flow to injured areas may also be involved in its neuroprotective effect.

Produces the most rapid onset of anaesthesia, but recovery is slower than with propofol.

Indications


Short surgical procedures, sole agent

Seizures, short term control

Cerebral protection

Raised intracranial pressure

Precautions

Contraindicated in:




- Allergy to barbiturates

- Porphyria

- Asthma – bronchospasm may occur

- Severe respiratory compromise – further respiratory depression occurs

Adverse Effects

Common

Transient erythema noted as lushing

Hypotension

Respiratory and myocardial depression

Prolonged somnolence with repeated doses

Infrequent

Laryngospasm, pain at injection site

Rare

Anaphylaxis, bronchospasm

Dosage

Adult (administered as a 2.5% solution (25mg/mL))

IV Bolus 3-5mg/kg according to response; additional injections of 25-50mg when needed

Drug Name Nitrous Oxide

Drug Class Anaesthetic (Inhaled)

Mode Of Action

Enhance the inhibitory ion channel activity and inhibit excitatory activity in the brain to induce hypnosis and amnesia, and in the spinal cord to cause immobility in response to painful stimuli

Indications

Induction and maintenance of general anaesthesia

Analgesia (in subanaesthetic concentrations)

Precautions

Contraindicated in:

- Myasthenia gravis – muscle weakness may increase

- Susceptibility to malignant hypethermia

- Vitamin B12 deficiency – increased risk of neurological dysfunction, inc. subacute combined degeneration of the spinal cord with prolonged exposure

Adverse Effects

Common

Shivering (independent of temperature)

Nausea and vomiting

Infrequent

Arrhythmias

Rare

Megaloblastic anaemia, leucopeia, agranulocytosis, neuropathy, myeloneuropathy (with prolonged or repeated use)

Dosage

Adult 70% with 30% oxygen (analgesia 25-50% with oxygen)

Drug Name Vecuronium

Drug Class Anaesthetic (Neuromuscular Blocker)

Mode Of Action

Indications

Precautions

Contraindicated in:

Adverse Effects

Common

Rare

Dosage

Adult

Drug Name Suxamethonium

Drug Class Anaesthetic (Neuromuscular Blocker)

Mode Of Action

Indications

Precautions

Contraindicated in:

Adverse Effects

Common

Rare

Dosage

Adult

Drug Name Clonidine

Drug Class Anaesthetic

Mode Of Action

Indications

Precautions

Contraindicated in:

Adverse Effects

Common

Rare

Dosage

Adult

Drug Name Cocaine

Drug Class Local Anaesthetic

Mode Of Action

Indications

Precautions

Contraindicated in:

Adverse Effects

Common

Rare

Dosage

Adult

Drug Name Lidnocaine

Drug Class Local Anaesthetic

Mode Of Action

Indications

Precautions

Contraindicated in:

Adverse Effects

Common

Rare

Dosage

Adult

CARDIOVASCULAR DRUGS

Drugs for Heart Failure

Aldosterone Antagonists

Eplerenone

Spironolactone

Loop Diuretics

Bumetanide

Ethacryic Acid

Frusemide

Sympathomimetics

Adrenaline

Dobutamine

Dopamine

Noradrenaline

Drugs for Angina and Acute Coronary Syndromes

Nitrates

Glyceryl Trinitrate

Isosorbide Dinitrate

Isosorbide Mononitrate

Other Antianginal Drugs

Ivabradine

Nicorandil

Perhexiline

Antihypertensives

Thiazide and Diuretics

Chlorthalidone

Hydrochlorothiazide

Indapamide

Potassium-Sparing Diuretics

Amiloride

Beta-Blockers

Atenolol

Bisoprolol

Carvedilol

Labetalol

Metoprolol

Oxprenolol

Pindolol

Propranolol

ACE Inhibitors

Catopril

Enalapril

Fosinopril

Lisinopril

Perindopril

Quinapril

Ramipril

Trandolapril

Calcium-Channel Blockers

Amlodipine

Diltiazem

Felodipine

Lercanidipine

Nifedipine

Nimodipine

Verapamil

Vasodilators

Diazoxide

Hydralazine

Minoxidil

Sodium Nitroprusside

Centrally Acting Hypertensives

Clonidine (see Anaesthetic Agents)

Methyldopa

Moxonidine

Non-Selective Alpha-Blockers

Phenoxybenzamine

Phentolamine

Selective Alpha-Blockers

Prazosin

TerazosinAntiarrhythmics

Adenosine

Amiodarone

Atropine

Digoxin

Disopyramide

Esmolol

Flecainide

Soprenaline

Lignocaine (see Anaesthetic Agents)

Mexiletine

Sotalol

Statins (Drugs fo Dyslipidaemia)

Atorvastatin

Fluvastatin

Pravastatin

Rosuvastatin

Simvastatin

Drug Name

Drug Class Anaesthetic

Mode Of Action

Indications

Precautions

Contraindicated in:

Adverse Effects

Common

Rare

Dosage

Adult

BLOOD AND ELECTROLYTES

Anticoagulants

Heparins

Dalteparin (LMWH)

Danaparoid

Enoxaparin (LMWH)

Heparin

Vitamin K Antagonists

Phenindione

Warfarin

Antiplatelet Drugs – antiplatelet drugs inhibit platelet aggregation, they are used in the management of arterial thrombosis (clots initially made of platelets), they are not used in management of VTE (fibrin clots)

Glycoprotein IIb/IIIa Inhibitors

Abciximab

Eptifibatide

Tirofiban

Other Antiplatelet Drugs

Aspirin

Clopidogrel

Dipyridamole

Ticlopidine

Thrombolytics

Alteplase

Reteplase

Streptokinase

Tenecteplase

Urokinase

Other Drugs Affecting Haemostasis

Vitamin K

Tranexamic Acid

Drugs For Anaemia

Folic Acid

Iron

Vitamin B12

Drug Name Heparin (standard or unfractionated), Dalteparin and Enoxaparin are LMWHs

Drug Class Anticoagulants

Mode Of Action

Inactivate clotting factors IIa (thrombin) and Xa by binding to antithrombin III, LMWHs have a much greater effect on Factor Xa than on thrombin.

Indications

Prevention of VTE and other thromboses in surgical and high risk medical patients

Treatment of VTE

Treatment of acute coronary syndromes

Treatment of peripheral arterial occlusion

Treatment of DIC

Precautions

Contraindicated in:

- Those with a risk of bleeding inc. thrombocytopenia, bleeding disorders (haemophilia), peptic ulcer, recent cerebral haemorrhage, severe uncontrolled hypertension, bacterial endocarditis, major trauma or recent surgery

- Renal impairment (use heparin rather than LMWH)


Adverse Effects

Common

Bleeding

Bruising and pain at injection site

Hyperkalaemia

Mild reversible thrombocytopenia

Infrequent

Transient elevation in liver aminotransferases, severe thrombocytopenia

Rare

Skin necrosis (at injection site), osteoporosis and alopecia with long term use, allergic reactions including urticaria

Dosage

Adult - Prevention (Heparin or Dalteparin)

SC 5000 units 2-3 times daily fr 7-10 days or until mobilised (medical high risk patients)

Drug Name Warfarin (Coumadin, Marevan)

Drug Class Anticoagulants, Vitamin K Antagonists

Mode Of Action

Inhibits synthesis of vitamin K-dependent clotting factors (II, VII, IX, X) and the antithrombotic factors protein C and protein S

Indications

Prevention and treatment of VTE (DVT, PE)

Prevention of thromboembolism in patients with prosthetic heart valves

Primary prevention of stroke in patients with AF associated with mitral valvulopathy and other risk factors

Secondary prevention of stroke in patients with AF

Prevention of thromboembolism before and after cardioversion for AF

Prevention of stroke in patients with previous MI and increased embolic risk

Precautions

Contraindicated in:

- Patients with high risk of bleeding – bleeding disorders, previous GI bleeding, haemorrhagic retinopathy, intracerebral aneurysm or haemorrhage, severe hypertension, bacterial endocarditis, frequent falls

- Caution in patients with renal and/or hepatic impairment

Surgery – it is safe to continue warfarin in people with high risk of thromboembolism where there is a low risk of significant bleeding, otherwise stop warfarin 4-5days before elective surgery to allow the INR to return to normal (give IV heparin or SC LMWH)

Adverse Effects

Common

Bleeding

Rare

Skin necrosis, purple discolouration of toes, allergic reactions, alopecia, fever, rash, nausea, vomiting, diarrhoea, hepatic dysfunction

Dosage

Adult usually 5mg daily for 2 days then adjust according to INR, usual maintenance dose 1-10mg daily

Drug Name Aspirin (acetylsalicyclic acid) (Aspirin, Cardiprin, Cartia, Aspro clear, Solprin, Astrix)

Drug Class Antiplatelet Agent

Mode Of Action

Inhibits platelet aggregation by irreversibly inhibiting cyclo-oxygenase, reducing the synthesis of thromboxane A2 (an inducer of platelet aggregation) for the life of the platelet

Indications

Acute MI

Unstable angina

Primary and secondary prevention of stroke and acute MI in patients with risk factors

Secondary prevention in ischaemic heart disease (angina, MI, after CABG)

Prevention of thromboembolism in non-rheumatic AF in low risk patients

Relief of pain, inflammation and fever

Precautions

Contraindicated in:


- Renal and/or hepatic impairment

Adverse Effects

Common

GI irritation

Asymptomatic blood loss

Increased bleeding time

Infrequent

Stevens-Johnson syndrome, toxic epidermal necrolysis, iron deficiency anaemia, GI haemorrhage

Rare

Intracranial haemorrhage, GI ulcer

Dosage

Adult

75-150mg daily is effective for long term use

150-300mg daily may be required in acute conditions

Drug Name Clopidogrel (Iscover, Plavix)

Drug Class Antiplatelet Drug

Mode Of Action

Inhibits bindig of adenosine diphosphate (ADP) to its platelet receptor, and the subsequent ADP-mediated activation of the glycoprotein IIb/IIIa complex, thereby inhibiting platelet aggregation

Indications

Prevention of vascaular ischaemic events in patients with symptomatic atherosclerosis (recent ischaemic stroke, recent MI, peripheral arterial disease)

Non-ST segment elevation acute coronary syndrome (with aspirin)

Adjuvant to reperfusion therapy for STEMI (with aspirin), unless acute coronary artery bypass grafting is likely

Precautions

Contraindicated in:


- Renal and hepatic impairment

Adverse Effects

Common

Bleeding

Diarrhoea

Rash

Infrequent

Intracranial bleeding, GI ulcer

Rare

Thrombotic thrombocytopenic purpur, aplatic anamia, thrombocytopenia, neutropenia, allergy including angioedema and Steven-Johnson syndrome

Dosage

Adult

75mg daily (preventive dose)

Drug Name Streptokinase (Streptase)

Drug Class Thrombolytics

Mode Of Action

Convert plasminogen to plasmin, which catalyses the breakdown of fibrin

Indications

Acute STEMI

Acute massive VTE in patients who are haemodynamically unstable

Peripheral arterial thromboembolism

Thrombosed IV cannulae, central venous catheters and haemodialysis shunts

Acute ischaemic stroke within 3 hours of onset of symptoms

Precautions

Contraindicated in:


- Hepatic impairment

Adverse Effects

Common

Hypotension

Bleeding (inc. at injection sites)

Intracerebral bleeding

Internal bleeding

Infrequent

Allergic reactions including fever, chills, rash, nausea, headache, bronchospasm, anaphylaxis, vasculitis, nephritis, hypotension

Rare

Cholesterol embolism

Dosage

Adult - Prevention (Heparin or Dalteparin)

Acute STEMI – 1500000 units over 30-60min (IV infusion)

DVT – 250000 units over 30min, then 100000 units/hr for 24-72 hours (IV infusion)

Drug Name Iron

Drug Class Drugs For Anaemia

Mode Of Action

Essential element required for the formation of haemoglobin and myoglobin

Indications

Prevention and treatment of iron deficiency anaemia

Treatment of iron deficiency anaemia in people on haemodialysis receiving epoetin

Precautions

Contraindicated in:

- Haemochromatosis

- Anaemia not due to iron deficiency


Adverse Effects

Common

Abdominal pain

Nausea

Vomiting

Constipation

Diarrhoea

Black discolouration of faeces

Dosage

Adult - (1mg of elemental iron is equivalent to 3mg ferrous fumarate, 3mg ferrous sulfate)

Treatment of iron deficiency – 100-200mg daily (orally)

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