Pharmacology - Drug Monographs

Important drug monographs
Originally from Garry, updated and formatted by Dan

For more detailed dosing information (but not pharmacokinetics) see the online Critical Care Drug Manual
Table of Contents
Adenosine...................................................................................................................................................................................................................... 3
Adrenaline ..................................................................................................................................................................................................................... 4
Amiloride ....................................................................................................................................................................................................................... 5
Aminophylline ................................................................................................................................................................................................................ 6
Amiodarone ................................................................................................................................................................................................................... 7
Amitriptyline ................................................................................................................................................................................................................... 8
Amoxycillin..................................................................................................................................................................................................................... 9
Amphetamine .............................................................................................................................................................................................................. 10
Aspirin ......................................................................................................................................................................................................................... 11
Atenolol ....................................................................................................................................................................................................................... 12
Atracurium ................................................................................................................................................................................................................... 13
Atropine ....................................................................................................................................................................................................................... 14
Bretylium ..................................................................................................................................................................................................................... 15
Bupivicaine .................................................................................................................................................................................................................. 16
Captopril ...................................................................................................................................................................................................................... 17
Carbamazepine ........................................................................................................................................................................................................... 18
Carbon......................................................................................................................................................................................................................... 19
Cefotaxime .................................................................................................................................................................................................................. 20
Cephalothin ................................................................................................................................................................................................................. 21
Charcoal ...................................................................................................................................................................................................................... 22
Chlorothiazide .............................................................................................................................................................................................................. 23
Chlorpromazine ........................................................................................................................................................................................................... 24
Cimetidine.................................................................................................................................................................................................................... 25
Ciprofloxacin ................................................................................................................................................................................................................ 26
Clonazepam ................................................................................................................................................................................................................ 27
Cocaine ....................................................................................................................................................................................................................... 28
Codeine ....................................................................................................................................................................................................................... 29
Colchicine .................................................................................................................................................................................................................... 30
Diazepam .................................................................................................................................................................................................................... 31
Digoxin ........................................................................................................................................................................................................................ 32
Dobutamine ................................................................................................................................................................................................................. 33
Dopamine .................................................................................................................................................................................................................... 34
Doxycycline ................................................................................................................................................................................................................. 35
Enoxaparin .................................................................................................................................................................................................................. 36
Erythromycin................................................................................................................................................................................................................ 37
Ethanol ........................................................................................................................................................................................................................ 38
Fentanyl ....................................................................................................................................................................................................................... 39
Flumazenil ................................................................................................................................................................................................................... 40
Fluoxetine .................................................................................................................................................................................................................... 41
Frusemide.................................................................................................................................................................................................................... 42
Gentamycin ................................................................................................................................................................................................................. 43
Glyceryl trinitrate .......................................................................................................................................................................................................... 44
Haloperidol .................................................................................................................................................................................................................. 45
Halothane .................................................................................................................................................................................................................... 46
Heparin ........................................................................................................................................................................................................................ 47
Hepatitis B Vaccine ...................................................................................................................................................................................................... 48
Indomethacin ............................................................................................................................................................................................................... 49
1
Insulin .......................................................................................................................................................................................................................... 50
Ipratropium .................................................................................................................................................................................................................. 51
Lignocaine ................................................................................................................................................................................................................... 52
Lithium ......................................................................................................................................................................................................................... 53
Magnesium .................................................................................................................................................................................................................. 54
Marijuana ..................................................................................................................................................................................................................... 55
Metoclopramide ........................................................................................................................................................................................................... 56
Midazolam ................................................................................................................................................................................................................... 57
Morphine ..................................................................................................................................................................................................................... 58
Na Bicarbonate ............................................................................................................................................................................................................ 59
Naloxone ..................................................................................................................................................................................................................... 60
Nitrous-Oxide ............................................................................................................................................................................................................... 61
Oxygen ........................................................................................................................................................................................................................ 62
Pancuronium ............................................................................................................................................................................................................... 63
Paracetamol ................................................................................................................................................................................................................ 64
Penicillin ...................................................................................................................................................................................................................... 65
Pethidine ..................................................................................................................................................................................................................... 66
Phenobarbital .............................................................................................................................................................................................................. 67
Phenytoin .................................................................................................................................................................................................................... 68
Prazosin ...................................................................................................................................................................................................................... 69
Prilocaine ..................................................................................................................................................................................................................... 70
Procainamide ............................................................................................................................................................................................................... 71
Prochlorperazine.......................................................................................................................................................................................................... 72
Promethazine .............................................................................................................................................................................................................. 73
Propranolol .................................................................................................................................................................................................................. 74
Propofol ....................................................................................................................................................................................................................... 75
Red Back Spider Antivenom ........................................................................................................................................................................................ 76
Salbutamol................................................................................................................................................................................................................... 77
Snake Antivenoms ....................................................................................................................................................................................................... 78
Sotalol ......................................................................................................................................................................................................................... 79
Spironolactone ............................................................................................................................................................................................................. 80
Streptokinase............................................................................................................................................................................................................... 81
Sumatriptan ................................................................................................................................................................................................................. 82
Suxamethonium ........................................................................................................................................................................................................... 83
Tetanus Immunoglobulin ............................................................................................................................................................................................. 84
Tetanus toxoid ............................................................................................................................................................................................................. 85
Thiopentone................................................................................................................................................................................................................. 86
Thioridazine ................................................................................................................................................................................................................. 87
t-PA ............................................................................................................................................................................................................................. 88
Trimethoprim ............................................................................................................................................................................................................... 89
Valproate ..................................................................................................................................................................................................................... 90
Vecuronium ................................................................................................................................................................................................................. 91
Verapamil .................................................................................................................................................................................................................... 92
Warfarin ....................................................................................................................................................................................................................... 93
Example Drug Monograph ........................................................................................................................................................................................... 94
2
Adenosine
HISTORY First discovered in the 1920’s
New uses rediscovered in the 1980’s
STRUCTURE/CLASS Endogenous nucleoside
PHARMACODYNAMICS Slows conduction through the AV node by blocking specific adenosine receptors.
Mechanism is increased K+ conductance and decreased cAMP induced Ca influx
ECG = increased PR interval
ABSORPTION IV with rapid absorption
DISTRIBUTION Most cells
METABOLISM Rapidly degraded by cells:

(a) Deaminated
(b) Phosphorylated
EXCRETION T½ = 10 seconds
INDICATIONS 1. SVT 90 - 95% effective conversion

2. Diagnosis of tachyarrhythmia
3. Adjunct to thalium scanning
CONTRAINDICATIONS Heart block 2nd or 3rd degree

Sick sinus
SPECIAL PRECAUTIONS Patients with asthma.
INTERACTIONS With theophylline it is ineffective - blocks adenoreceptors

Potentiated by Dipyridamole and Carbamazepine.
ADVERSE EFFECTS Flushing

Dyspnoea
SOB
Panic / sense of impending doom.
DOSING/ADMINISTRATION IV - through central line 3-6 mg

Increased dose if peripheral 6-12mg
TOXICOLOGY Self limiting T½ of 10 seconds
WITHDRAWAL SYNDROMES
3
Adrenaline
HISTORY
STRUCTURE/CLASS Catecholamine - endogenous Benzene ring + ethyl amine.
PHARMACODYNAMICS Binds to alpha and beta receptors which act through G proteins resulting in effector events.
Beta leads to stimulation of cAMP production. Alpha leads to inhibition of cAMP.
Main effects:
1. Relaxes smooth muscle of bronchi
1. Cardiac stimulation
2. Skeletal muscle vascular dilatation
ABSORPTION Oral absorption is poor - oxidised and conjugated in gut.

SC/ I M/ I V rapid onset and short duration.
Inhaled.
DISTRIBUTION Crosses placenta.

Does not cross the blood brain barrier.
METABOLISM Terminated by metabolism in sympathetic nerve ends via COMT> MAO paths.
Metabolites = VMA / MOPEG (excreted in kidney but inactive.)
EXCRETION Kidney metabolites inactive.

Half life = 1-3 mins.
INDICATIONS 1. Anaphylaxis / allergy -cardiovascular and mast cell effects.

2. Arrest - facilitates CPR via vasoconstriction.
3. Anaesthetics - prolongs local anaesthetic and decreases bleeding.
4 Asthma -inhaled /SC.
5. Croup
6. Decrease mucus membrane secretion
CONTRAINDICATIONS IHD Pheochromocytoma

Hypertension Glaucoma
Hyperthyroid.
SPECIAL PRECAUTIONS With local anaesthetic in fingers, toes and ears.
INTERACTIONS With other drugs that act at alpha and beta receptors.
Halothane.
Tricyclics, amphetamine, MAOIs - increased responsiveness but COMT still degrades.
ADVERSE EFFECTS Cerebral haemorrhage. Increased BP.

Arrhythmia. Local ischaemia.
Apprehension
DOSING / ADMINISTRATION IM / SC / IV or inhaled.

Start with 0.1-0.5 mg.
Aqueous solution 1 : 1000, 1 : 10,000
TOXICOLOGY Can be reversed depending on system but VERY short acting.

NB - vasoconstriction of fingers
1. Phentolamine
2. Vasodilators
4
Amiloride
HISTORY First approved for use in 1967.
STRUCTURE/CLASS Potassium sparing diuretic amiloride hydrochloride

Not an aldosterone antagonist.
Consist of a guanidinium group containing a pyrazine derivative.
A moderately strong base.
PHARMACODYNAMICS Reduces Na+ absorption in collecting tubules and ducts and inhibits tubular secretion of K+
therefore increases Na+ / K+ excretion ratio.
ABSORPTION Not metabolised by liver, excreted unchanged by kidneys. peak plasma levels in 3-4 hrs.
plasma half life = 6-9 hrs.
DISTRIBUTION Not to be given IV causes hypertension and ECG changes.
METABOLISM Nil in liver.
EXCRETION Excreted 50% in liver unchanged. rest in faeces.
INDICATIONS Used to spare potassium when other diuretics are the main agents.
Congestine heart failure and hypertension.
Hepatic cirrhosis with ascites.
CONTRAINDICATIONS Hyperkalaemia.
Anuria.
Diabetic nephropathy.
Severe progressive renal disease.
SPECIAL PRECAUTIONS Other forms of K+ supplementation.

Impaired renal function.
Metabolic or respiratory acidosis.
Diabetes. Elderly. Gout. Pregnancy.
INTERACTIONS Decreases clearance lithium.

Risk of hyperkalaemia with ACE inhibitors.
ADVERSE EFFECTS Minor only - Nausea, anorexia, abdo pain.
DOSING/ADMINISTRATION Oral tablet 5 mg

10 -20 mg daily in single or divided doses.
TOXICOLOGY Rare - supportive measures.
5
Aminophylline
HISTORY
STRUCTURE/CLASS Methylxanthine. Compound of theophylline (79%) + ethylenediamine. has actions and uses
of theophylline but is used when greater solubility in water is required, particularly for
injections.
PHARMACODYNAMICS Bronchodilator in reversible airways obstruction, also causes diuresis, CNS and cardiac
stimulation and gastric acid secretion by blocking phosphodiesterase. Increases tissue
concentrations of cAMP which promotes catecholamine stimulation of lipolysis,
glycogenolysis and gluconeogenesis. Induces release of adrenaline from adrenal medulla.
Adenosine receptor antagonist.
ABSORPTION Depends on formulation. Can be up to 100% orally absorbed.
DISTRIBUTION Loading dose determined on basis that 600 microgms aminophylline per kg bodyweight can
be expected to increase the serum theophylline concentration by approximately 1
microgram /ml and serum concentration of 10-20 microgm/ml is required.
METABOLISM In liver by demethylation and oxidation.

Half life extremely variable and dependent upon age, liver function, cardiac function, lung
disease and smoking.
EXCRETION 10% in urine as unchanged drug.

Neonates up to 50% unchanged in urine.
INDICATIONS Bronchospasm.
CONTRAINDICATIONS Uncontrolled arrhythmias, hyperthyroidism, peptic ulcers, uncontrolled seizure disorders.

Hypersensitivity to xanthines or any component.
SPECIAL PRECAUTIONS Peptic ulcer / hyperthyroidism / hypertension / tachyarrhythmias and compromised

cardiac function.
Do not inject I V at faster than 25 mg / min.
INTERACTIONS Multiple ----Smoking, diet, charcoal, phenytoin, phenobarb, barbiturates, loop diuretics etc
all decrease theophylline levels. Cirrhosis, CHF, fever, propranolol, erythromycin,
cimetidine, OC pill, calcium channel blockers increase theophylline levels.
ADVERSE EFFECTS Nausea, vomiting, insomnia, irritability, tachycardia, seizures, circulatory failure, abdo pain,
agitation, muscle cramp, tremor.
DOSING/ADMINISTRATION Injection --25mg/ml. Tablet = 100 mg / 200 mg. Slow release = 225mg.
Oral liquid = 105mg /ml. Suppository = 250mg / 500mg.
TOXICOLOGY Nausea, vomiting, seizures, insomnia, irritability.

Repeat doses of charcoal unless ileus present.
Amenable to charcoal haemoperfusion.
6
Amiodarone
HISTORY Originally developed as an antianginal.
STRUCTURE/CLASS Class I, II, III, IV antiarrhythmic.

Benzofuran derivative which is iodinated ( structurally similar to thyroxine)
PHARMACODYNAMICS Blocks inactive Na+ channels (Class I )

Blocks K+ channels - prolongs AP ( Class III )
Blocks Ca++ channels ( Class IV )
Non-competitive alpha 1 and beta adrenergic inhibitor ( Class II )
Cardiac effects: 1) Prolongs AP therefore increased RP and increased QT and QRS.
2) Antianginal via beta blocker effects and Ca++ channel blocking effects.
Extracardiac effects: 1) Vasodilatation
2) Alpha I and beta blocking effects
ABSORPTION Oral absorption is incomplete and erratic ( individual variability )

Bioavailability 22 - 86 % ( first pass metabolism in gut and liver )
DISTRIBUTION Strong protein binding.

half life is 20 - 100 days.
Vd is high --- adipose tissue / heart / highly perfused organs.
METABOLISM Biotransformation to desethylamiodarone - longer half life ( activity unknown)
EXCRETION Hepatobiliary
? Enterohepatic circulation
INDICATIONS Antiarrythmic for supraventricular arrhythmias / ventricular arrhythmias /

tachyarrhythmias in WPW.
Antianginal in Europe / South America.
CONTRAINDICATIONS Sinus bradycardia ( all degrees of heart block with episodic bradycardia )
Hypotension and circulatory collapse.
Breast feeding and pregnancy.
Thyroid dysfunction.
SPECIAL PRECAUTIONS Teratogenic.

U waves and abnormal T waves ( are non toxic )
Heart failure (add diuretics )
High doses cause bradycardia and conduction disturbances ( especially with elderly /
digoxin)
INTERACTIONS Digoxin - leads to increased digoxin levels.

Warfarin - leads to increased INR.
Beta blockers / Ca++ channel blockers lead to bradycardia.
ADVERSE EFFECTS Corneal microdeposits / Pulmonary alveolitis / photosensitivity / Raised LFTs / Rarely
hepatotoxicity / thyroid dysfunction ( hyper or hypo ) / metallic taste.
Neuro : peripheral neuropathy / headaches / ataxia / nightmares / vertigo / tremor /
nausea / vomiting.
DOSING/ADMINISTRATION Oral: 200mg tab: initially high dosing as slow onset, no acute toxicity (eg. ii TDS for 1/52
then ii BD for 1/52 then i BD for 1/52 then i mane)
IV: 5 mg / kg I V in 5% dextrose in 20 mins -- 2 hrs. ( max = 1200mg / day)
TOXICOLOGY Supportive measures for hypotension / bradycardia.

Activated charcoal.
May need beta adrenergic stimulants or glucagon.
WITHDRAWAL SYNDROMES Effects last for 3 months ( half life = 100 days)
7
Amitriptyline
HISTORY Based on the prototypical TCA imipramine. Approved for use in in 1961 for depression
STRUCTURE/CLASS Tricyclic antidepressant
PHARMACODYNAMICS Blocks NA and 5-HT (5-HT >> NA ). Initial increase in NA and 5HT causes decrease in cAMP
leading to eventual down-regulation of beta receptors causing a clinical response. Initial
firing of neuron decreases and eventual result is a normal firing rate.
Potent muscarinic blocker , antagonises also α1, H1 and H2
ABSORPTION Well orally. delay due to decreased gastric emptying secondary to anticholinergic effect.
T max I M = 5 - 10 mins. T max PO = 60 mins.
Half life = 10 - 50 hrs ( average = 16 hrs)
DISTRIBUTION 93 - 95 % protein bound. Vd = 14 L / kg Lipophilic - not dialysable.
METABOLISM Liver N - demethylation + ring hydroxylation produce active metabolites.

NB - nortriptyline.
EXCRETION Urine 60% several days of active and inactive metabolites. Faeces 10% Bile.
INDICATIONS Depression (endogenous and reactive ) with sedative effects.

Nocturnal enuresis.
Chronic pain / migraine prophylaxis / trigeminal neuralgia / acute panic attacks /
phobic anxiety attacks.
CONTRAINDICATIONS MAOIs -- hypertension / hyperpyrexia / convulsions.

Acute M I.
Known hypersensitivity.
Pregnancy / lactation
SPECIAL PRECAUTIONS Seizures / mania / suicide / liver dysfunction / narrow angle glaucoma .
Anticholinergic : urinary retention / prostatic hypertrophy.
Hyperthyroid / thyroid meds - monitor.
Stop before elective surgery.
Arrythmias / conduction defects.
INTERACTIONS Additive anticholinergic effect with antihistamine / Parkinson / psychotic drugs.

Hepatic enzyme inducers eg phenobarb / smoking.
Cimetidine / OC increases effect / sympathomimetic agents eg adrenaline in local
anaesthetic and ephedrine in cold meds result in HPT. Antihypertensive clonidine blocked.
ADVERSE EFFECTS CNS - oversedation / confusion / seizure / peripheral neuropathy.

CVS - Hyper and hypotension / arrhythmia / conduction defect / M I / CVA.
Skin allergies/ SLE / bone marrow depression / agranulocytosis / galactorrhoea /
gynaecomastia.
Tolerance develops.
DOSING/ADMINISTRATION PO 75 mg increasing to 150mg. Max = 300 mg/day

I M / I V 20 - 30 mg 4x daily. Elderly = 25 -50 mg OD.
Eneuresis: 6 - 12 yrs 10 - 25 mg / day. >12 yrs =25 - 50 mg / day
TOXICOLOGY >1000 mg toxic. --- agitation / delirium / seizure / coma /arrhythmia / conduction defect
/ respiratory depression / hyperpyrexia / metabolic acidosis / bladder and bowel paralysis
/ wide QRS and long ST .
Tachyarrythmia - propranolol ; Bicarb; KCL ; anticonvulsant.
NOT procainamide.
WITHDRAWAL SYNDROMES Abrupt stopping nausea / headache. Irritability / dream and sleep disturbances.
Not addictive,
8
Amoxycillin
HISTORY As per history of discovery of penicillin.
STRUCTURE/CLASS Part of penicillin family of antibiotics. Has a thiazolidine ring attached to a beta lactam ring
that carries a secondary amine group. Weak acids.
PHARMACODYNAMICS Selective inhibitors of bacterial cell wall synthesis. Binds to cell receptors on bacteria,
inhibiting transpeptidation and peptidoglycan synthesis is blocked.
Bactericidal agents.
ABSORPTION Oral bioavailability = 93% well absorbed from gut.

relatively stable to gastric acid.
To minimise binding to food best taken one hour before or after food.
DISTRIBUTION Distibuted widely through body fluids and tissues.

Lipid insoluble - doesn’t enter cells well.
18% plasma protein bound. Vd = 15L /70 kg
METABOLISM Half life = 1.7 hrs.

Not appreciably metabolised.
EXCRETION 86% excreted in kidney unchanged. 10% excreted by glomerular filtration, 90% excreted by
tubular secretion to max of 2g/hr in adult.
INDICATIONS Broad spectrum antibiotic (inactivated though by beta lactamases)

Gram -ve and + ve cover. For upper and lower respiratory infections / soft tissue infections
/skin infections / prophylaxis endocarditis.
CONTRAINDICATIONS Previous hypersensitivity to`penicillins - all cross react and cross sensitise.
SPECIAL PRECAUTIONS 1. infectious mononucleosis - rash.

2. renal failure
3. hypersensitivity to cephalosporins.
INTERACTIONS 1. Excretion is delayed by probenecid -which blocks tubular secretion.

2. May interfere with OC pill metabolism.
ADVERSE EFFECTS 1. GI disturbance.

2. Allergy - anaphylaxis / serum sickness / skin rash /oral lesions /vasculitis.
3. maculopapular rash.
4.Nephritis /granulocytopenia (rare)
I M / I V - can cause pain at injection site.
DOSING/ADMINISTRATION P O / I M /I V . Oral pead drops at 125mg /1.25 ml. Syrup is 125mg or 250 mg /5 mls. Caps
are 250mg or 500mg
Adult 250 -500mg tds. Paed 25-50 mg /kg /day in 3 doses.
TOXICOLOGY OD generally isn’t life threatening - GI upset most likely adverse effect presuming that the
patient isn’t sensitive to penicillins.
9
Amphetamine
HISTORY First used in 1932 for nasal congestion - vasoconstrictor
Increasing popularity as a pep pill and now has limited legitimate use
STRUCTURE/CLASS Non catecholamine sympathomimetic agent

Basic, with incr. pKa.
PHARMACODYNAMICS Alpha and Beta effects from release of neurotransmitter from synaptic vesicles NOT direct
stimulation of receptors.
Block catachol re uptake - inhibit monoamine oxidase
ABSORPTION High oral availibility
DISTRIBUTION High lipid solubility and crosses the blood / brain barrier
METABOLISM Hepatic metabolism
EXCRETION pH dependent excretion. Alkaline pH increases the T½ in urine.
INDICATIONS 1. Narcolepsy
2. Attention deficit
3. Obesity
CONTRAINDICATIONS 1. Hypertension
2. Hyperthyroid
3. Glaucoma
SPECIAL PRECAUTIONS Dependance
INTERACTIONS Increased toxicity with MAO inhibitors
ADVERSE EFFECTS 1. Dependence - elevated mood and feeling of wellbeing

2. Hypertension - CVA
DOSING/ADMINISTRATION IV
Oral 10 - 30 mgs (child 0.1 - 0.5mg / kg)
Requires an increasing dose as there is tolerance
TOXICOLOGY Overdose leads to hyper-reactivity, seizures, hallucinations, all of which are extensions of
the effect.
WITHDRAWAL SYNDROMES Dependence withdrawal :

 ravenous appetite
 mental depression
 exhaustion
10
Aspirin
HISTORY Acetylsalicylic acid. Willowbark - active ingredient = salicin--- salicylic acid
STRUCTURE/CLASS Non-opiod analgesic. Synthesized 1853.

NSAID. Used from 1899
PHARMACODYNAMICS 1. ASA binds irreversibly to cyclooxygenase: salicylate reversibly at low dose decreases
platelet TxA2: higher dose, tissue prostacyclin.
2. Inhibits kallikrein system (via inhibition kallikrein mediated PG)
3. Analgesic i) decreased inflammatory mediators ii) ? subcortical site
4. Antipyretic i) vasodilatation ii) decreased IL-1 by macrophages: decreased
hypothalamic response
ABSORPTION 1. Absorbed rapidly in stomach (acid pH) and also duodenum.

2. High mucosal cell concentration - leads to damage.
3. 3. Buffering gastric pH > 3.5 decreases irritation.
DISTRIBUTION 1. Absorbed as ASA, hydrolyzed to acetic acid and salicylate (blood and tissue esterase).
2. Bound to albumin - increased serum concentration - increased free salicylate.
METABOLISM 1. Mostly conjugated with glucuronide and glycine by liver.

2. Analgesic/antipyretic dose 600-1200mg / d. First order kinetics - half life 3 - 5 hours.
3. Anti-inflammatory dose > 4g / d . Zero order kinetics - half life > 15 hours due to
saturation of hepatic enzymes.
EXCRETION Renal excretion - increased by alkalinizing urine.
INDICATIONS 1. Analgesia 2. Anti-inflammatory 3. Anti-pyretic

4. Platelet inhibition 5. Recurrent miscarriages 6. HELP syndrome
Primary and secondary prophylaxis: MI , TIA, CABG
CONTRAINDICATIONS Haemophilia ? Reye’s syndrome
SPECIAL PRECAUTIONS Gastritis/ulceration may be controlled with misoprostol (PGE 1)
INTERACTIONS 1. Increased risk salicylate intoxication with acetazolamide.

2. EtOH increased risk GI bleeding.
3. Displaces from protein binding - phenytoin, tolbutamide, methotrexate.
4. Decreased activity spironolactone.
5. Decreased tubular secretion penicillin.
ADVERSE EFFECTS 1. GI effects - gastritis, ulceration, vomitting ( large dose - central effect).
2. Salicylism - tinnitus, vertigo, decreased hearing ( usually chronic intoxication).
3. Low dose decreased secretion uric acid. High dose increases secretion - uricosuric.
4. Decreased GFR via decreased PGI 2
5. Confusion, fever, dehydration with increased dose.
DOSING / ADMINISTRATION Analgesic / antipyretic = 300 - 600mg PO q 3-4 hrs

Anti-inflammatory = 4g/d (adults)
TOXICOLOGY Serious intoxication > 150-175mg/kg

1. Respiratory alkalosis
 Peripheral: Increased CO2 produced by skeletal muscle
 Central: Stimulates medullary respiratory centre → ↑ RR and VT
2. Renal compensation for resp alkalosis.
3. Further metabolic acidosis
 Salicylic acid dissociation → ↑ H+
 Deranged CHO metabolism leads to ↑ lactic, pyruvic, and acetoacetic acid
 ↓ Vasomotor function → ↓ Renal function and ↑ PO4/SO4 levels.
11
Atenolol
HISTORY Developed for use as a safer drug than non-selective beta antagonist
STRUCTURE/CLASS Beta 1 - selective antagonist with no intrinsic agonist activity

Hydrophilic
PHARMACODYNAMICS Effective concentraction is lmg / l

Acts on beta 1 receptors - i.e. cardiac effects - reduction in heart rate, blood
pressure
ABSORPTION 56% oral availability
DISTRIBUTION 5% plasma bound. Minimal CNS penetration
METABOLISM Very little first pass. Half life = 5-7 hrs

Minimal metabolism usually excreted unchanged
EXCRETION 94% excreted unchanged in urine.
INDICATIONS Hypertension. Used with elderly with isolated systolic hypertension.

Post MI decrease mortality in first week.
Angina, migraine prophylaxis, anxiety.
CONTRAINDICATIONS Conjestive cardiac failure - but new studies show low dose may be given.
SPECIAL PRECAUTIONS Renal failure - accumulation of drug

Bronchospasm
Peripheral vascular disease
IDDM. Aged (reduced excretion)
INTERACTIONS Beta 1 agonists
ADVERSE EFFECTS Bradycardia

Hypotension
Bronchospasm (in spite of select activity) - hyperglycaemia
DOSING ADMINISTRATION 50 - 100MG / day. Once daily dose given orally

IV 2.5 - 5mgs over 5 minutes.
TOXICOLOGY Effects on heart may be reversed by atropine
WITHDRAWAL SYNDROMES Rebound hypertension, increased angina, arrhythmias with abrupt discontinuation.
12
Atracurium
HISTORY
STRUCTURE/CLASS Isoquinolone non depolarising neuromuscular blocker.
PHARMACODYNAMICS Blocks transmission of motor nerve impulses to striated muscle receptors. ACh
blocker therefore prevents access of the neurotransmitter to its receptor and
prevents depolarisation.
Can intubate within 90 secs.
ABSORPTION IV only
DISTRIBUTION Its main breakdown product, laudanosine, readily crosses blood brain barrier.
METABOLISM Broken down by spontaneous inactivation (Hoffman elimination), non enzymatic,

therefore not dependant on renal or hepatic mechanisms,as breakdown products are
inactive. Laudanosine is very slowly metabolised by liver and has a long half life
(150 mins)
EXCRETION Termination not dependant on liver,kidney or circulatory function.
INDICATIONS muscle relaxation for intubation.

Obstetric anaesthesia.
CONTRAINDICATIONS Previous reaction to drug.
SPECIAL PRECAUTIONS Shocked patient -- may lead to decreased BP.

Frail,cachectic or elderly.
In neonates and patients with myestenia gravis or other neuromuscular disorders.
Not fully tested in pregnancy.
INTERACTIONS
ADVERSE EFFECTS Seizures - laudanosine crosses blood brain barrier.

Histamine release skin flushing,hypotension, bronchospasm.
DOSING / ADMINISTRATION IV only. Adults 0.3-0.6 mg/kg.(gives block for 15-30 mins) Suppementary doses 0.1-
0.2 mg/kg prn
Paeds >1/12 - same as adult/kg dose.
TOXICOLOGY Reversed by neostigmine (+ atropine)

Reversal measured by the restoration of tetanic response to 95% of normal
neuromuscular function.
13
Atropine
HISTORY Used for thousands of years in poisons, cosmetics, medicines. smoked as a remedy for asthma. Found
in Atropa Belladonna (deadly nightshade). Used in renaissance as pupillary dilator for women. Also
in Datura stramonium, used in various forms for its hallucinogenic effects.
STRUCTURE/CLASS Naturally occurring compound. Closely structurally related to scopolamine and homatropine. Tropic
acid. Base = tertiary amine.
PHARMACODYNAMICS Reversible blockade of all types of muscarinic receptors and competitive antagonist of
cholinomimetics. Blocks exogenous agonists more effectively than endogenous Ach.
Tissue sensitivity salivary, bronchial sweat glands > smooth muscle , heart >> gastric parietal cells.
Potency at nicotinic receptors much less. Undetectable at clinical doses, seen at toxic doses.
ABSORPTION Well absorbed from gut, conjunctival membranes.
DISTRIBUTION Wide - Vd = 120L/70kg

50% bound to protein, rapidly removed from blood
Half life (alpha) = 2 hours with significant CNS levels within 30-60mins
Half life (beta) = 4.3 hours.
METABOLISM Oral bioavailability. 50%. Hepatic metabolism - hydrolysis, conjugation products.
Effect on all organs declines quickly except in eye: mydriasis, cycloplegia 7-10/7
EXCRETION Clearance = 24.6L/70kg/hr.
60% of IV dose excreted unchanged in urine.
INDICATIONS 1. Symptomatic bradycardia/ second degree heart block/ over active vagal tone
2. Pre-anaesthetic (IV) to decrease bronchial secretions and laryngospasm
3. Uviteis / keratitis/ iritis/ cyclitis
4. Poisoning by: carbamates/ organophosphates/ nerve gases/ inocybe mushrooms
CONTRAINDICATIONS Glaucoma (angle closure) / GI obstruction/ paralytic ileus/ intestinal atony/ severe colitis/
megacolon/ diarrhoea secondary to enterotoxin - producing bacteria / myasthenia gravis / allergy/
hypersensitivity/ acute haemorrhage/ jaundice
SPECIAL Shallow anterior chamber/ BPH/ hyperthermia/ hyperthyroidism/ CHD/ autonomic neuropathy/
PRECAUTIONS advanced hepatorenal disease / elderly/ pregnancy/ lactation/ severe electrolyte or fluid imbalance
/ proven GU.
INTERACTIONS Anticholinergic effects enhanced by TCAs / antipsychotics/ antihistamines/antiparkinsons

Increased degredation L-dopa ingut causes worsening of symptoms of parkinsons.
Lomotil: additive effects with CNS depressants/ hypertensive crisis with MAOIs
ADVERSE EFFECTS Eye: prolonged blurred vision/mydriasis/ cycloplegia/ conjunctival irritation (rare).
Other : Dry mouth/hypohydrosis + hyperthermia (death as little as 2mg in children) constipation/
dizziness + orthostatic hypotension/ tachycardia/urinary retention/impotence/ allergic reactions.
DOSING / Oral: 0.6mg. IV: 0.3 - 1.2mg (most often 0.6mg). Eye: 0.5%, 1% as SO4.
ADMINISTRATION Eye: 1d, repeat 5mins + 1-2d after 30mins prn. Bradycardia: 0.3-0.6mg repeat up to q5/60.
TOXICOLOGY  Red as a beet → Hyperpyrexia

 Blind as a bat → Eye effects (mydriasis, cycloplegia)
 Mad as a hatter → CNS stimulation, delirium, agitation
 Dry as a bone → Reduced sweat production
 Dry mouth
 Urinary retention
 Tachycardia
Treatment : charcoal, no bright lights, active cooling, fluids and vasopressors for decreased BP,control
seizures with diazepam. Use cholinesterase only if hyperthermic or very rapid SVT e.g. physostigmine
(controversial).
WITHDRAWAL Potential rebound effects from long-term use.

SYNDROMES Nausea, vomitting, diarrhoea, abdo cramps, salivation, sweating, miosis, bronchial constriction
Lomotil - diarrhoea
14
Bretylium
HISTORY Originally introduced as an antihypertensive
STRUCTURE/CLASS Class III Antiarhythmic

Quaternary amine
PHARMACODYNAMICS Decr. adrenergic activity by decreased NA release by decreasing excitability

Prolong AP incr. refractory period
* Initially release catecholamine --> positive inotropic effect
ABSORPTION Oral poor (quaternary amine) 20%

IV/ IM only
DISTRIBUTION 6 litre / kg
METABOLISM NIL
EXCRETION Renal excretion without Metab 80%

T½ - 8 hrs
INDICATIONS VF cardiac arrest which has failed to respond to initial therapy. VT.
May be the antiarrhythmic of choice in hypothermia.
CONTRAINDICATIONS No contraindication as used in lifethreatening events
SPECIAL PRECAUTIONS 1. Renal failure

2. Fixed cardiac output patients e.g. Aortic stenosis
INTERACTIONS Digoxin
ADVERSE EFFECTS Hypotension is significant - keep patient supine

Nausea / vomiting
Bradycardia incr. arrythmia
DOSING / ADMINISTRATION 5 - 10 mg / kg over 10 mins IV
TOXICOLOGY Extension of clinical effects
WITHDRAWAL SYNDROME
15
Bupivicaine
HISTORY Cocaine - Nermann 1860. Clinical use Keller 1884 ( eye anaesthetic )
Procaine - Einhorn 1905.
Lignocaine - Luffgren 1943 most popular.
STRUCTURE/CLASS Long acting amide local anaesthetic.

16x potency Procaine.
4x potency Lignocaine.
PHARMACODYNAMICS 1 Mechanism of action : Blocks Na+ channels (activated and unactivated ) -voltage and
time dependant.
2 Action on nerves : Blocks pain fibres type C and type B first. - dependant on fibre
diameter / firing frequency and position in nerve bundle.
3 Dose dependant arrythmic effect in low dose is an antiarrythmic.
ABSORPTION I V / SC. Greater lipid solubility than lignocaine.

Absorption rate is dependant on dose / concentration /rate of administration /
vascularity.
DISTRIBUTION 95% bound to plasma proteins.

Peak blood levels after epidural nerve block = 30 - 45 mins.
Half life = 3-5 hrs (relatively long)
METABOLISM liver conjuation with glucuronic acid.
EXCRETION kidney excreted - 5% in unchanged form.
INDICATIONS Post op analgesia.

Nerve blocks.
Obstetric anaesthesia.
CONTRAINDICATIONS Allergy / hypersensitivity to amide local anaesthetics.

Uncorrected hypotension ( epidural / spinal )
I V regional blocks ( toxic systenic effects )
SPECIAL PRECAUTIONS Avoid I V dosing / accumulation with repeated dosing / renal impairment leads to
accunulation / pregnancy /
malignant hyperthermia / hypotension / bradycardia / conduction disturbances / digoxin
intoxication.
INTERACTIONS Antiarrthymics of amide local anaesthetic type.
ADVERSE EFFECTS Allergy / CNS excitation / nervous / dizzy / blurred vision / tremor - drowsy -
convulsions - loss of consciousness - respiratory arrest.
Effects of local nerve block.
CVS cardiotoxic - peripheral easodilation/ hypotension / myocardial depression
/bradycardia /arrest.
DOSING/ADMINISTRATION No greater than 2 mg /kg or 400 mg /day. No more frequent than 3 hourly.
2-30% mls of 0.5 Marcain dependant on site / size of nerve / type of block.
TOXICOLOGY Adequate ventil;ation.

Seizure control.
Cardiac resuscitation + antiarrythmics for arrythmias eg VF.
16
Captopril
HISTORY Venoms of pit vipers contain ACE inhibitors
STRUCTURE/CLASS An ACE inhibitor, also (same enzyme) increases bradykinin levels

An analogue of a dipeptide
PHARMACODYNAMICS Inhibits conversion of angiotensin I to ang II. Increased bradykinin levels lower BP
by decreasing systemic vascular resistence and mean diastolic and systolic BP.
Systemic arteriolar vasodilation, increases compliance of large arteries.
Causes regression of LV hypertrophy in hypertensive patients.Retards loss of renal
function in diabetic nephropathy.
It reduces peripheral vascular resistence with no alteration in cardiac output
ABSORPTION Rapidly asorbed orally, 95% bioavailability. Food reduces oral availability by 25 -
30%. Therefore take 1 - 2 hrs before meals.
DISTRIBUTION Vd = 0.81L/kg. Most body tissues but not CNS.

Blood levels correlate poorly to clinical response.
METABOLISM half life = 2 hrs. Metabolised mainly by liver to disulphide conjugates.
EXCRETION Urine 50% unchanged.
INDICATIONS Hypertension - 50% monotherapy control in mild - moderate hypertension.

LVF - increases life expectancy unless contra indicated, given to all with LVF.
Diabetic nephropathy, sclerderma
CONTRAINDICATIONS Acute renal failure

Pregnancy (foetal effects in 2nd & 3rd trimester)
SPECIAL PRECAUTIONS Heart failure, salt depleted (as these have high Ang II levels thus are
hyperresponsive)
INTERACTIONS Diuretics augment effect by rendering BP renin dependent.
Hyperkalaemia occurs with captopril and K + sparing diuretics, K+ supplements or
NSAIDs
Increase plasma digoxin levels
ADVERSE EFFECTS Well tolerated. No metabolic side effects. Hypotension, especially with 1st dose.
Cough - 5 - 20%. Skin rash. Proteinuria.
Angioneurotic oedema. Dysgeusia.
Rarely neutropenia. Can cause acute renal failure.
DOSING/ADMINISTRATION 6.25 - 50mg tds. Oral dosage.
TOXICOLOGY Severe hypotension on 1st dose especially in hypovolaemic patients.
17
Carbamazepine
HISTORY
STRUCTURE/CLASS Anti epileptic / neurotropic / psychotropic

tricyclic compound derivitive of iminostilbene
Chemical structure similar to imipramine and other TCA
Also similar to phenytoin in 3D spatial terms
PHARMACODYNAMICS Mechanism is only partially understood but is similar to phenytoin.

Blocks voltage sensitive Na channels to inhibit high frequency repetitive firing.
Acts presynaptically to decrease synaptic transmission.
Also interacts with adenosine receptors - ? significance
Also inhibits uptake and release of noradrenaline from brain synaptogenes which appears
to be independent of the GABAergic system.
ABSORPTION Oral - slow and erratic but eventual almost complete absorption.
Peak is usually in six to eight hrs. Syrup gives a higher peak level than the same dose of
tablet.
Can slow absorption by having after a meal to tolerate larger daily doses.
DISTRIBUTION Wide. Slow. Vd 1L / kg
[CSF] correlates [ free in plasma]
70% bound to protein but no displacement of other drugs are observed.
METABOLISM Completely metabolized by liver via conjugation or hydroxylation.
There is an active metabolite formed conjugation pathway called 10, 11 epoxide which has
anticonvulsant activity.
EXCRETION Regular users of carbamazepine induce microsomal enzymes which reduce the half life .
Half life is 10-20 hrs for long time patients and much longer for first time patients.
INDICATIONS Anti-epileptic - partial seizures (drug of choice)

- generalized tonic/ clonic
Neurotropic - trigeminal neuralagia, alcohol withdrawal, diabetes insipidus.
Psychotropic - affective disorders.
CONTRAINDICATIONS Hypersensitivity to carbamazepine or TCAs.

AV block MAOI use
previous bone marrow suppression. Acute intermittent porphyria.
SPECIAL PRECAUTIONS Need to monitor haematological hepatic and renal function

Glaucoma (mild anticholinergic)
Driving and machinery (drowsiness)
Pregnancy - monotherapy preferred, folic acid supplement
INTERACTIONS Induces microsomal enzyme system leading to increased metabolism of primidone /

phenytoin / ethosuximide / valproate / clonazepam / OC pill.
Valproate, propoxyphene and troleandomycin inhibit carbamazepine clearance.
Phenytoin and phenobarbitone induce metabolism of carbamazepine.
ADVERSE EFFECTS Diplopia and ataxia most common. Hyponatraemia and water intoxication have occurred.
Mild GI upset, vertigo, idiosyncratic blood dyscrasias.
Drowsiness at high doses hypersensitivity - rash / eosinophilia. Liver toxicity rare.
DOSING / ADMINISTRATION Syrup - 100mg / 5mls Tablet - 200 & 400mg CR tablet - 200 & 400 mg
Children - 15 -25 mg/kg / day Adults 1-2g /day. Start at 200mg bd
Therapeutic range - 4-8mcg / ml in sample prior to morning dose.
TOXICOLOGY Urine retention and water intoxication.

Stupor / coma / convulsion / respiratiory/ depression / tachycardia/ hypo or
hypertension/ wide QRS
WITHDRAWAL SYNDROMES Will need cover with another anti-epileptic compound if is abruptly stopped.
18
Carbon Monoxide
HISTORY
STRUCTURE/CLASS Colourless,odourless, non irritant gas from incomplete combustion of organic matter.
Specific gravity 0.97 relative to air (does not stratify)
PHARMACODYNAMICS 1. Binds to Hb with high affinity (220 x O2 affinity). This results in decreased carriage of
oxygen and decreased dissociation of oxygen from the other three sites on Hb i.e. it
shifts the curve to the left.
2. May bind to cytochrome P450 and cytochrome A3 to inhibit cytochrome oxidase
system and cause neurological disturbance
ABSORPTION Inhaled and absorbed by lungs.

Dose is dependent upon concentration and length of exposure
DISTRIBUTION Widely distributed

10 - 15% will be extravascular bound mainly to myoglobins which dissociate slower than
COHb causing rebound increase in COHb during treatment.
Crosses placenta (delayed).
METABOLISM Very small amount is oxidized to CO2.

COHb is very stable even after death.
EXCRETION Exhaled by lungs. Elimination half life = 320min in air

Elimination half life = 80 min in 100% O2
Elimination half life = 20min in hyperbaric O2
SOURCES Endogenous - breakdown of protoporphyrin producing bilirubin and CO.

Therefore increased in haemolytic anaemia / pregnancy / menstruation.
Exogenous - incomplete combustion of organic fuels .
Certain paint removers contain methylene chloride which produces CO in liver.
CONTRAINDICATIONS
SPECIAL PRECAUTIONS Threshold limit values TWA - 25ppm

Average concentration CO = 0.1ppm, heavy traffic CO concentration may be > 100ppm.
SMOKERS Normal non smoking adults have < 1% of total Hb in form of COHb
Smokers have 5-10% of total Hb in COHb form
ADVERSE EFFECTS Tissue hypoxia - brain and heart most vulnerable.

1. Psychomotor impairment.
2. Headache and temporal tightness, cutanous vaso dilatation
3. Tachycardia, tachypnoea, syncope and coma
4. Deep coma, convulsion , shock, respiratory failure
Large individual variability between exposure and effects.
PEOPLE MORE AT RISK Anaemia - less Hb available to begin with

Children - increased metabolic rate - need more O2
Altitude - decreased atmospheric O2 - increased effect.
TOXICOLOGY Treatment - remove from source / 100% Oxygen / hyperbaric oxygen
Factors - concentration / duration of exposure/ [Hb] / metabolic rate
WITHDRAWAL
SYNDROMES
19
Cefotaxime
HISTORY As per cephalothin
STRUCTURE/CLASS Third generation cephalosporin.
PHARMACODYNAMICS Cell wall synthesis inhibitor in bacteria.

Major feature of the third generation cephalosporins is their expanded gm -ve cover.
ABSORPTION Not orally absorbed - given parenterally.
DISTRIBUTION Penetrates body tissues and fluids well and achieves good levels in CSF.
Half life = 1 - 1.7 hrs.
METABOLISM metabolised to a desacetyl metabolite in liver, this metabolite is active against a

similar spectrum of bacteria.
EXCRETION Excreted in kidney - glomerular filtration and tubular secretion.

20 - 30 % drug excreted unchanged in urine.
INDICATIONS Broad spectrun - gm-ve and gm +ve cover. Anaerobes = surgical prophylaxis.
1. Active against meningitis - H influenzae /pneumococcus / meningococcus/ enteric
gm -ve rods - not Pseudomonas
2 Sepsis of unknown cause in immunocompronised patients.
CONTRAINDICATIONS Previous hypersensitivity to cephalosporins.
SPECIAL PRECAUTIONS Pregnancy.

Severe renal impairment.
Penicillin allergy.
INTERACTIONS Excretion is delayed by probenecid.
ADVERSE EFFECTS Hypersensitivity reactions.

Diarrhoea / candidiasis / rash / leucopenia / thrombocytopenia / eosinophilia -
rarely phlebitis,suprainfection.
DOSING/ADMINISTRATION I M / I V cefotaxime sodium prep = 0.5,1 and 2 gm vials. Give 1 gm I V / I M 12

hourly.
In severe infection give 1 gm 8 hourly . Surgical prophylaxis give 1 gm I V / I M
immed prior to surgery.
TOXICOLOGY Supportive measures in OD.
20
Cephalothin
HISTORY From cephalosporium fungi. Resemble penicillin, but variably resistant to beta
lactamases.
STRUCTURE/CLASS First generation cephalosporin.
PHARMACODYNAMICS Bind to specific penicillin binding proteins on bacteria. block transpeptidation hence
inhibiting cell wall synthesis.Activate autolytic enzymes in cell wall which results in
bacterial death.
ABSORPTION Not absorbed fron gut so must be given I V . Water soluble.
DISTRIBUTION Half life = 57 mins.

I V penetrates most tissues well excluding the CNS.
METABOLISM Not appreciably metabolised by liver.
EXCRETION 52% excreted unchanged by kidney - mainly by glomerular filtration and tubular
excretion.
INDICATIONS Broad spectrum cover. Gm +ve >> gm -ve bacteria / some anaerobes are sensitive.
Can be used for surgical prophylaxis and in dialysis and cystic fibrosis patients.
CONTRAINDICATIONS Previous hypersensitivity to cephalosporins.
SPECIAL PRECAUTIONS Previous sensitivity to penicillins as cross allergenicity between penicillin and
cephalosporins =6 - 15 %
Marked renal impairment.
Pregnancy.
INTERACTIONS Increased risk of nephrotoxicity with aminoglycosides and potent diretics.

Excretion is delayed by probenecid.
ADVERSE EFFECTS Diarrhoea - pseudomembranous colitis (rare)

Hypersensitivity reactions - anaphylaxis / skin rash / nephritis /haemolytic anaemia
/granulocytopenia.
Local reaction to injection.
DOSING/ADMINISTRATION I V injection - as powder for reconstitution. Can give 1-2 gm 4-6 hourly I V for severe
infection.
0.5 - 1 gm 4-6 hourly for less severe and children 80 - 160 mg / kg / day in divided
doses.

Haemodialysis / haemoperfusion may be considered ti increase elimination of drug.
21
Charcoal
HISTORY
STRUCTURE/CLASS Chemical adsorbent
PHARMACODYNAMICS Adsorbs drugs and chemicals to the surface of charcoal particles (almost irreversibly).
Can interrupt the enterohepatic circulation of drugs and therefore increase excretion (TCA,
glutethimide).
Can enhance the rate of diffusion of chemical into GI tract lumen.
ABSORPTION Not absorbed
DISTRIBUTION N/A
METABOLISM N/A
EXCRETION Excreted in faeces
INDICATIONS Treatment of poisoning with drugs it is able to adsorb.
CONTRAINDICATIONS Does not bind iron, lithium or K+ (FeLiK = the cat).

Not useful for corrosives ( acid or alkaline), boric acid, alcohols, methylcarbamate,
tolbutamide.
Unprotected airway
SPECIAL PRECAUTIONS Binds alcohols and cyanide poorly
INTERACTIONS
ADVERSE EFFECTS Constipation (raraly bowel obstruction)

Aspiration pneumonitis
20-30% incidence of charcoal induced vomiting in conscious patients
DOSING / ADMINISTRATION Give orally or via a gastric tube if required

Should try to get a charcoal : drug ratio of 10:1
TOXICOLOGY Repeated dosing is of value in poisoning due to : carbamazepine / dapsone / digoxin / β

blockers / phenobarbitol / theophylline /
22
Chlorothiazide
HISTORY Developed from sulfanilamide an early microbial drug that caused a Sodium bicarbonate
diuresis.
STRUCTURE/CLASS Benzothiadiazides. series of heterocyclic rings with an unsubstituted sulfonamide group. Has
some carbonic anhydrase inhibitory action.
PHARMACODYNAMICS Inhibits Na Cl reabsorption from the luminal side of the epithelial cells in the distal convoluted
tubule.
Seems to be an electrically neutral Na Cl cotransporter distinct from the one in the Loop of
Henle.
Active reabsorption of Ca++ in the distal convoluted tubule.
ABSORPTION Site of absorption in gut not known.

Approx 25% is absorbed orally ( less lipid soluble)
DISTRIBUTION
METABOLISM No known metabolites.
EXCRETION Rapidly eliminated by kidney.

Actively secreted by renal tubules.
INDICATIONS Hypertension.
Congestive heart failure.
Nephrolithiasis due to hypercalcaemia.
Nephrogenic diabetes insipidus.
CONTRAINDICATIONS Anuria.
Sensitivity to sulphonamides.
SPECIAL PRECAUTIONS Driving - restict alcohol intake.

Electrolyte imbalance.
Impaired renal function.
Hepatic disease.
May cause hyper uricaemia.
INTERACTIONS Risk hyperkalaemia with K+ sparing diuretics.

Alcohol, barbiturates, narcotics - can cause orthostatic hypotension.
Antidiabetic medications /corticosteroids.
ADVERSE EFFECTS Gastric irritation / orthostatic hypotension.

Hyponatraemia /hypokalaemia
Hyperglycaemia / hyperuricaemia.
Photosensitivity rashs
DOSING / ADMINISTRATION Tablet 500 mg 250 - 1000 mg daily.
TOXICOLOGY Depression of serum K+

No other toxic effects.
Supportive measures.
23
Chlorpromazine
HISTORY First antipsychotic effective in schizophrenia.
STRUCTURE/CLASS Phenothiazine neuroleptic with aliphatic side chain.
PHARMACODYNAMICS Dopaminergic system. Dopamine antagonist . blocking α1 = 5-HT2 > D2 > D1.
As for Haloperidol. Chemoreceptor trigger zone leads to inhibition and antiemetic
activity.
Low clinical potency / medium extrapyramidal toxicity /high sedative and
hypotensive effect.
ABSORPTION Rapid oral. Low bioavailability due to first pass effect. 30% bioavailable.
T max I M = 30 min. T max 0-2 hrs. Half life = 30 hrs.
DISTRIBUTION 95 - 98 % protein bound (85% albumin)

Well distributed , lipophilic. Accumulates in brain and lung.
Vd = 20L / kg.
Crosses placenta.
METABOLISM Liver: Via hepatic microsomes. Hydroxylation and demethylation then conjugation.
Elimination in 2 phases: Rapid 2 hrs, slow 50 hrs
About 60 metabolites, some active /some inactive.
EXCRETION Faeces and urine (equally)
INDICATIONS Schizophrenia / psychosis esp paranoia / mania / psychomotor - agitation /

schizoaffective disorder / intractable hiccoughs / induction of hypothermia
Antiemetic in terminal disease. Intractable hiccup
Perioperatively as adjunct to anaesthesia. Inhibits shivering.
CONTRAINDICATIONS Epilepsy / Parkinson’s / coma / CNS depression / Liver or renal dysfunction /

cardiac failure / myasthenia gravis / prostatic hypertrophy / hypothyroidism /
Glaucoma
Bone marrow depression.
SPECIAL PRECAUTIONS Sunscreens - photosensitivity.

Avoid direct contact - contact dermatitis.
Caution : elderly ( hypothermia ) Pregnancy ( prolongs labour)
Lactation - it crosses into milk.
I M postural hypotension - keep patient supine.
INTERACTIONS CNS depressants - potentiated / antihypertensives - potentiated / anticholinergic

potentiated eg tricyclics. Antagonises antiparkinsonian drugs.
Antacids decrease absorption. Decreased hypoglycaemic agent response.
Decreased convulsive threshold therefore increase antiepilepsy meds.
ADVERSE EFFECTS Sedation / pseudodepression / confusional states / parkinsonism / acute dystonic

reactions tardive dyskinesia / orthostatic hypotension / arrhythmia / wide QT / ST
depression / T changes/ resp depression / Decreased WBC / agranulocytosis /
dermatitis / obstructive jaundice / lens and corneal opacification / gynaecomastia /
impotence.
DOSING / ADMINISTRATION PO start 25 mg TDS gradual increase, lowest possible dose. IM deep 25-50 mg 3-4x
in 24 hrs. IV dilute , protect from light.
TOXICOLOGY Sedation / hypotension / arrhythmia etc.

Monitor. Hypotension warm IV fluids use Dopamine. AVOID lignocaine / adrenaline.
Dystonic reaction use benztropine. Neuroleptic malignant syndrome use
bromocriptine.
24
Cimetidine
HISTORY Derived from histamine in mid-1970s as first derivatives too toxic.
STRUCTURE/CLASS H2-antagonist.
PHARMACODYNAMICS Competes for H2 receptors mainly at gastric parietal cells. No significant H1 mediated action.
H2 receptors also on cardiac muscle, mast cells, brain.
GIT: decreases HcL secretion 80-90% inhibition of basal secretion 4-5hrs after single dose,
decreases volume of gastric secretion, temporary decrease of the concentration of pepsin,
little effect on other GI secretions or smooth muscle
Unrelated to H2 blockade inhibition of P450 oxidase, decreased renal clearance of basic drugs
secreted in renal tubule, decreased hepatic bloodflow. All three of these cause numerous
interactions, the first is the most important
Also binds to androgen receptors therefore anti-androgen effects.
ABSORPTION Rapid oral absorption peak levels in 45-90mins.

Not affected by food or antacids.
PO / IV IM give comparable therapeutic blood levels
DISTRIBUTION Plasma binding 19-22% Vd = 70L/70kg
METABOLISM Oral bioavailability approx. 70%

Hepatic metabolism. Clearance = 32.4L/70kg/hr.
EXCRETION 62-70% excreted renally unchanged therefore decreased dose in renal failure.
Half life (beta) = 1.9hrs (1.5-2.3 hrs). Increased in severe renal failure,
19% excreted as sulphoxide = major metabolite.
Small amounts unchanged in faeces.
INDICATIONS Treatment of DU + benign GU - healing and control of symptoms of acute episodes / GORD +
erosive oesophagitis/ recurrent ulceration/ conditions where decreased Hcl useful/
Prevention stress ulcer in ill patients at risk of haemorrhage/ Treatent of hyper-secretory
states / to decrease gastric acidity and secretory volume and risk of pulmonary damage from
aspiration especially in pregnant patients undergoing GA for LUSCS.
CONTRAINDICATIONS Hypersensitivity.
SPECIAL PRECAUTIONS Decreased renal function /avoid rapid IV injection especially in CV disease/ lactation and
pregnancy/ many drug interactions/ May mask symptoms and allow transient healing of Ca -
therefore beware patients in middle age or older with new or recently changed dyspepsia.
INTERACTIONS 3 mainmechanisms for decreased metabolism/clearance

Decreased metabolism causes increased serum levels of benzodiazepines (except oxazepam,
temazepam, lorazepam)/ betablockers - those with hepatic metabolism = propranolol,
metoprolol, labetolol / lignocaine/ phenytoin / quinidine/ warfarin/ TCAs/ theophylline/
caffeine/ EtOH / carbamazepine / metronidazole.
ADVERSE EFFECTS Mild and transient diarrhoea, tiredness/ diziness/ rashes (sometimes severe)/ confusional
states (esp. elderly, ill, rare, reversible)/ depression/ headache/ gynecomastia (men) /
galactorrhoea (women)/ decreased sperm count/ impotence (v high doses, reversible)/
slurred speech/delirium/ IM - transient pain at injection site.
DOSING / ADMINISTRATION PO : 200mg, 400mg, 800mg. Inj : 200mg/2ml.

GI : up to 1600mg/day (divided)/ up to 12g/d for hypersecretory states/
IV 200mg/100ml over 30min q4-6h
Paracetomol OD : 40mg/kg in DS or N-saline over 1 hr.
TOXICOLOGY Charcoal
Treatment symptomatic
WITHDRAWAL SYNDROMES Nil reported. Potentially rebound hyperacidity and reversal of drug interactions.
25
Ciprofloxacin
HISTORY Nalidiixic acid = first quinolone discovered in 1963. - was excreted too rapidly for systemic
effect. Ciprofloxacin was developed from Nalidixic acid.
STRUCTURE/CLASS Fluorinated analogue of nalidixic acid.

quinolone antibiotic.
PHARMACODYNAMICS Blocks bacterial DNA synthesis by inhibiting DNA gyrase thus preventing the relaxation of
supercoiled DNA that is required for normal transcription and duplication.
Inhibit gm -ve rods / pseudomonas / neisseria.
ABSORPTION Well absorbed after oral administration. absolute bioavailability = 70%.
DISTRIBUTION Distributed widely to body fluids and tissues.

Half life = 4 hrs.
Vd = 130L / 70kg.
METABOLISM Nil significant first pass metabolism.

<20% of dose is metabolised by the liver.
EXCRETION Primarily renal ( tubular secretion and glomerular filtration.)
INDICATIONS Lower respiratory tract infections / UTIs / gonococcal urethritis : cervicitis / gastroenteritis
/ skin infections / bone and joint infections / biliary tract infections / gynae infections /
typhoid infections.
CONTRAINDICATIONS Hypersensitivity to ciprofloxacin or other quinolones.
SPECIAL PRECAUTIONS Renal impairment

Prepubertal children / pregnancy / elderly patients
Epileptic patients / patients with CNS disorders.
INTERACTIONS Theophylline - may increase plasma concs of theophylline.

Interferes with metabolism of caffeine.
Cipro + antacids /iron / sucralfate / may decrease the absorption of cipro.
Cipro + probenecid = 50% reduction ofrenal clearance of Cipro.
Enhances the effect of oral anticoagulants.
ADVERSE EFFECTS Mild GI disturbances - diarrhoea / nausea. -- colitis (rare)

CNS stimulation - tremor / restlessness / lightheadedness / headache.
Damage growing cartilage / anaphylactoid reactions / abnormal LFTs
DOSING / ADMINISTRATION Take 1-2 hrs before or 4 hrs after antacid / iron preparations PO.
250 - 750mg B.D. orally, 200 - 300mg B.D. IV.

< 10% cipro is removed from body after haemodyalysis or peritoneal dialysis.
26
Clonazepam
HISTORY
STRUCTURE/CLASS Benzodiazepine.
PHARMACODYNAMICS Same as for midazolam.

Acts as GABA receptor.
ABSORPTION Well orally. 90% bioavailable.

T max = 4 hrs.
half life = 18 - 40 hrs
DISTRIBUTION 85% protein bound.

Vd = 3L / kg . Lipophilic.
Therapeutic blood levels 20 -80 mg / ml.
METABOLISM Liver oxidative hydroxylation, reduction of 7 nitro group and formation of 7 amino and
acetylamino compounds. 4 metabolites, little activity.
major metabolite = 7 amino clonazepam.
EXCRETION Metabolites.
Urine 50-70%
Faeces 10-30%
INDICATIONS Epilepsy - children -- myoclonic and atonic seizures.

Primary and secondary tonic- clonic seizures.
Status epilepticus alt to diazepam.
CONTRAINDICATIONS As for diazepam.

Clonazepam ampoules contain benzyl ETOH - - can cause permanent neuropsychiatric
deficits in neonates.
SPECIAL PRECAUTIONS Hypersensitivity.

As for diazepam.
INTERACTIONS Additive to CNS depressants.

Increases phenytoin levels.
Liver enzyme inducers accelerate biotransformation.
ADVERSE EFFECTS Depression / drowsiness / fatigue / paradoxical hyperactivity / headache / muscle weakness
/ salivary and bronchial hypersecretion in infants / increased seizures in certain forms of
epilepsy / rashes / decreased libido / premature secondary sexual characteristics
DOSING / ADMINISTRATION PO 1 mg nocte increasing every 2-4 weeks to a max of 20 mg /day.

I V 1 mg slowly, max = 13 mg
Children PO 0.05 mg / kg increasing to max of 0.3 mg / kg
TOXICOLOGY Tiredness / ataxia / coma / resp depression / circulatory collapse .

Monitor. I V fluids.
DO NOT use flumazanil as this will produce seizures.
27
Cocaine
HISTORY Used many centuries by Peruvians: chewed leaves of Erythroxylon Coca = source of cocaine
for feeling of well being and fatigue reduction.
Isolated by Niemann 1860: introduced to clinical use by Koller 1884. Use in opthalmology as
anaesthetic despite strongly addicting CNS actions but only LA available for 30 years
STRUCTURE/CLASS Ester LA indirect-acting sympathomimetic.

Related to amphetamines, with benzene group + alkylamine - highly potent. Increased
dependancy potential and risk of death from OD.
PHARMACODYNAMICS 1. Amphetamine/ sympathomimetic actions: blockade of central and peripheral trans-

membrane re-uptake transporters of NA, dopamine, 5-HT. Rapidly enters CNS rapid onset of
effect. Peripheral sympathomimetic effects due to increased levels of circulating adrenaline,
NA and increased NA at nerve terminals.
2. LA actions : 50% potency of lignocaine. Short duration of action blocks AP generation and
impulse conduction along nerve axons. Blocks pain sensations and sympathetic
vasoconstrictor impulses.
ABSORPTION Rapidly absorbed from mucous membrane of nasopharynx and tracheobronchial tree
(medical and abuse use) .
Vasoconstrictor therefore decreased systemic absorption.
DISTRIBUTION Especially if taken IV or smoked rapidly enters CNS with rapid onset of effect.
Also distributed to cardiac muscle and peripheral nerves.
METABOLISM Hydrolysed by tissue, blood, esterases (e.g. butyrylcholinesterase) and due to bulky structure
also metabolized in liver.
Abuse effects last one hour: LA effects medium duration.
EXCRETION Renal
INDICATIONS Used topically in nasopharyngeal surgery because of LA+ vasoconstrictor effect.

May be used cautiously with adrenaline also used to decrease nasopharyngeal haemorrhage
and also topically in opthalmology
CONTRAINDICATIONS See precautions
SPECIAL PRECAUTIONS Cardiovascular disease / hypertension/ TCA use and current use of other sympathomimetics /
seizure disorders/ pregnancy.
INTERACTIONS Potentially increased heart rate, blood pressure, angina given with TCAs or other
sympathomimetics, catecholamines and others e.g. ephedrine, phenylephrine, amphetamine,
methylphenidate, tyramine.
ADVERSE EFFECTS Allergy to ester anaesthetics/ PABA derivatives / allergic reactions in a small number of
people / hypertension + seizures with high doses/ necrosis of nasal septal mucosa.
Fetus - advers effects all trimesters with increased spontaneous abortion.
DOSING / ADMINISTRATION Topical use : as paste / eye drops.

As drug of abuse : available as Hcl salt -- alkalinised, extracted with non-polar solvent--
freebase - “crack”. Sniffed or for more rapid intense effect smoked or used IV.
With IV heroin = “speedball”.
TOXICOLOGY Hypertension - treatment propranolol or Ca channel blocker, seizures - diazepam or

thiopentone (NOT phenytoin) or phenobarbitone + O2, NaHCO3, airway protection and
hyperventilation to prevent hypoxeima / acidosis.
WITHDRAWAL Symptoms possibly due to supersensitivity of inhibitory receptors on dopaminergic neurons

SYNDROMES causing intense craving; possibly withdrawal syndrome for foetus of addict once delivered.
Experimentally bromocriptine has reduced craving.
28
Codeine
HISTORY
STRUCTURE/CLASS Mild to moderate opioid agonist with one of the O H groups replaced by a CH3.
PHARMACODYNAMICS Acts via opioid receptors.

Analgesic effect due to conversion to morphine.
Antitussive effect is probably due to different receptors.
ABSORPTION High oral : parenteral potency.

Decreased first pass effect.
DISTRIBUTION Rapidly leaves the circulation and concentrates in highly perfused tissues.
Crosses blood brain barrier.
METABOLISM Metabolised in the liver.
EXCRETION Metabolite excreted by kidneys.

Half life = 2-4 hrs.
INDICATIONS Analgesia.
Antitussive.
CONTRAINDICATIONS Respiratory depression.
SPECIAL PRECAUTIONS Respiratory depression.

Paralytic ileus.
INTERACTIONS Ethanol. CNS depressant drugs.
ADVERSE EFFECTS Tolerance /dependance / constipation / nausea / vomiting / respiratory depression.
DOSING / ADMINISTRATION PO 30-60 mg 4 hourly ( max = 240 mg / day)

Parenteral 30-60 mg I M 4 hourly
TOXICOLOGY Respiratory depression.
Cardiovascular collapse.
WITHDRAWAL SYNDROMES Similar to other narcotics.
29
Colchicine
HISTORY Isolated from autumn crocus flower that grew in colchisin in Asia Minor
Benjamin Franklin was one of its first users in the USA.
STRUCTURE/CLASS Unique anti-inflammatory agent selective for gout.

It is an alkaloid.
PHARMACODYNAMICS Gout - Does not influence renal excretion of urate or blood concentration of urate.
Binds to micro-tubular protein to interfere with mitotic spindle function therefore inhibits
migration of leukocytes to inflamed area to reduce the release of lactate and pro-inflammatory
enzymes from phagocytosis.
Can arrest cell division - especially cells which have highest rate of cell division (also seen with
vinca alkaloids).
ABSORPTION Oral - rapid and peak plasma level in 2 hours.
DISTRIBUTION Predominantly to GI tract - also kidney, liver and spleen

Heart skeletal muscle and brain relatively spared.
METABOLISM Extensive hepatic deacetylation .
EXCRETION Predominantly faeces.

Urine 10-20% - increased inliver disease
Half life = 90minutes
INDICATIONS Prevent and abort acute attacks of gout during initiation of allopurinol or uricosuric agent.
Prevents attacks of mediterranean fever / ? sarcoid arthritis / ? hepatic cirrhosis
CONTRAINDICATIONS
SPECIAL PRECAUTIONS Elderly

Debilitated
GI ulceration
INTERACTIONS
ADVERSE EFFECTS Well tolerated in moderate dose

Nausea / vomitting / diarrhoea / abdo pain - most common earliest adverse effects. Can be
minimized by IV dosage.
Temporary leukopenia followed by leucocytosis (bone marrow effect)
Chronic use - increased risk of agranulocytosis, aplastic anaemia, myopathy, alopecia, ?
azospermia (described)
DOSING / ADMINISTRATION 0.5 and 0.6mg tablets. 0.5mg/ml solution.

Initial dose - 0.6 to 1.2 mg then 0.6mg every two hours until pain has gone or GI symptoms
appear. Total dose needed is about 4-10mg. Should not exceed 10mg. Should not repeat
course within 3 days to avoid accumulative toxicity.
‘Prophylactic dose varies from 0.5mg 1-3 times daily
TOXICOLOGY Haemorrhagic gastroenteritis/ extensive vascular damage / nephrotoxicity / muscle

weakness / ascending paralysis of CNS.
Treatment is supportive , drug is not removed by haemodialysis.
20g potetially lethal
30
Diazepam
HISTORY
STRUCTURE/CLASS Benzodiazepine.
Long lasting.
PHARMACODYNAMICS Same as for midazolam.

Acts as GABA receptor.
ABSORPTION Readily and completely orally absorbed.

T max = 30 - 90 min.
Half life of diazepam = 20 -40 hrs. Half life of desmethyldiazepam = 40 -140 hrs.
Therefore half life has little relationship to parent drug.
DISTRIBUTION Lipid soluble.
94 - 98 % protein bound.
Vd = 1.1 L / kg.
METABOLISM Liver phase 1 = microsomal oxidation to active metabolites ( 4 metabolites)

To desmethyldiazepam --- oxazepam --- temazepam.
Phase 2 = conjugation to glucuronides.
EXCRETION Urine.
INDICATIONS Premedication / antianxiety.

Anticonvulsant -- status epilepticus.
Muscle relaxant -- tetanus.
Dts -- ETOH withdrawal.
CONTRAINDICATIONS Oversedation in elderly / pulmonary disease / impaired renal function /acute narrow angle
glaucoma / anxiety secondary to depression / hepatic disease.
SPECIAL PRECAUTIONS Avoid in pregnancy and lactation. Cleft palate / neonatal withdrawal syndrome.
Prior to labour can cause floppy infant syndrome.
Breast milk secretion - can cause immature hepatic metabolism and lethargy.
Patient info : psychomotor skill impairment / avoid ETOH / addiction.
INTERACTIONS Additive CNS depressant effects.

Aminophylline antagonist.
Cimetidine / OC pill inhibit liver metabolism and increase effect.
ADVERSE EFFECTS Oversedation / depression / confusion / ataxia /slurred speech / paradoxical reaction causing
acute hyperexcitability / aggression and rage / physical and psychological dependance /
hypotension / constipation / blurred vision and diploplia / urinary retention
DOSING / ADMINISTRATION Premed : 0.1 - 0.2 mg / kg I V or oral. Epilepsy : 0.15 - 0.25 mg / kg I V repeat 30 mins.
Rectal - 10 mg and repeat in 10 mins.
Tetanus : 0.1 - 0.3 mg / kg I V repeat 1 - 4 hourly.
Acute panic attack and Dts :10 mg I V 5 mg / min 4 hourly. PO 2 mg tds max = 30 mg/d
Children: 0.2mg/kg I V .<5yrs = 5mg. >5yrs = 10mg. PR <3 yrs =5mg >3yrs =10mg.
TOXICOLOGY As for midazolam.
WITHDRAWAL SYNDROMES As for midazolam.
31
Digoxin
HISTORY Known to ancient Egyptians 3,000 years ago. 18th Century William Withering published a
monograph on effects of an extract of Digitalis purpurea (foxglove)
STRUCTURE/CLASS Steroid nucleus and unsaturated five membered lactose ring

Cardiac glycoside
PHARMACODYNAMICS Inhibits Na+ / K+ ATP ase which results in an increased intracellular Ca 2+ concentration.
(May also increase Ca2+ entry to cell and release from sarcoplasmic reticulum). At low
dose range parasympathomimetic effects predominate. At toxic levels sympathetic
outflow is increased. Also has direct effect on membrane of cardiac cells.
ABSORPTION 70 - 75% bioavailibility. 10% of people harbour bacteria which inactivate digoxin.
DISTRIBUTION Widely distributed to tissues including CNS. Plasma protein binding is 20-40%. Highest
concentrations are in the heart, kidney and liver. Vd = 6.3 L/kg.
METABOLISM Less than 20% metabolised. Largely excreted unchanged by kidneys.

T½ = 40 hrs.
EXCRETION Total clearance correlates with creatinine clearance
INDICATIONS Right or left sided CHF. In AF to decrease AV conduction and slow ventricular rate.
CONTRAINDICATIONS Only absolute contraindication is a patient who is already toxic
SPECIAL PRECAUTIONS Smaller doses in renal impairment. Hypokalemia sensitises heart to digoxin. (also
hypomagnesemia and hypercalcemia).
INTERACTIONS Most important is hypokalemia from diuretics. Amphotericin B, and corticosteriods may
cause hypokalemia. Reserpine and phenytoin cause bradycardia. Absorption is decreased
with antiacids and bile acid binding resins.
Interacts with most other antiarrhythmics.
ADVERSE EFFECTS Anorexia, nausea, vomiting and diarrhoea. Disorientation, hallucinations, abnormal colour
perception, gynaecomastia.
DOSING/ADMINISTRATION LD = 15 mgs / per kg in three divided doses over 12 hrs. Maintenance is 0.025 - 0.25 mg
daily.
Onset IV is max @ 2 hrs and orally max @ 4-6 hrs.
TOXICOLOGY OD is treated with Fab fragments of digitalis anitbody.

Bradycardia, ectopic beats, bigeminy, VT and heart block. Give potassium, phenytoin,
atropine.
WITHDRAWAL SYNDROMES No withdrawal syndrome
32
Dobutamine
HISTORY
STRUCTURE/CLASS Synthetic catecholamine - beta 1 selective (some alpha 1 and beta 2).
Beta 1 sympathomimetic
Structure similar to dopamine but has a bulky aromatic on the amino group.
PHARMACODYNAMICS Beta 1 agonist - direct inotrope / mild chronotrope / mild hypertensive / augments
conduction velocity through AV node (not atria).
Increases SV , increases CO , decreases LVFP, decreases systemic and pulmonary resistence.
Partial tolerance develops during prolonged continuous infusion (72 hrs) - this is down
regulation.
ABSORPTION Not effective orally.

IV - onset of action 1-2 mins.
Up to 10 mins for steady state and peak effect.
DISTRIBUTION Vd = 20% of body weight (or 0.2L/kg )
METABOLISM Rapid liver metabolism.

Principally methylation followed by conjugation.’
Plasma half life 2-4 mins.
Plasma clearance 59mls/min / kg
EXCRETION Urine - 3-0-methyldobutamine/ other conjugates.

Bile.
INDICATIONS Inotropic support in hypotensive cardiac failure - patients with abnormally increased LVFP
Sulphite sensitivity.
SPECIAL PRECAUTIONS Do not improve haemodynamics in most mechanical obstruction to ventricular filling or
outflow or both (cardiac tamponade, AS).
May increase HR or arterial BP.
Increased AV conduction will make atrial fibrillation worse.
May induce arrythmia
INTERACTIONS Combine with vasodilators in IHD potentiates and maintains the HR x BP product.
Increased CO - decreased systemic vascular resistance / decreases ventricular filling pressure.
Combine with dopamine - increased systemic arterial pressure, increased renal blood flow to
prevent decreased LVFP.
ADVERSE EFFECTS Increased HR 5-15 bpm / increased BP 10-20 mmHg systolic / increased ventricular ectopics
by 5% / hypotension/ phlebitis/ nausea /headache/ angina / SOB / palpitations/ decreased
K+
DOSING / ADMINISTRATION Continuou IV infusion. Short half life,therefore no loading dose needed 2.5-10 mcg/kg/min
TOXICOLOGY Anorexia / nausea/ vomitting/ tremor/ anxiety/ palpitations / headache/ SOB/

hypertension/ tachyarrhythmia / MI / VF/
Treatment - support - propranolol or lignocaine for arrythmia.
Pregnancy not well tested.. Can be used with care in children
33
Dopamine
HISTORY
STRUCTURE/CLASS Dihydroxyphenethylamine hydrochloride.

Immediate metabolic precursor of noradrenaline.
PHARMACODYNAMICS Activates D1 receptors in vascular beds leading to vasodilatation in several vascular beds
(renal vascular bed important clinically)
Activates presynaptic D 2 receptors to decrease noradrenaline release.
Activates beta 1 receptors in heart .
Low doses dopamine effects dominate, intermediate doses get increasing beta effect.
ABSORPTION For I V injection only.
DISTRIBUTION Not studied in humans. No info on protein binding.
METABOLISM Deamination by monoamine oxidase.

Formation of methylated and reduced derivatives by catechol - o - transferase.
Note : 25% synthesised to noradrenaline.
EXCRETION 97% appears in urine as metabolites.

70% of infused dose is excreted per 10 mins of infusion period.
Half life = 2 mins.
INDICATIONS Acute hypotension / shock associated with M I / endotoxic septicaemia / trauma / renal
failure .
Adjunct after open surgery where there is hypotension.
Chronic cardiac decompensation as in CHF.
Symptomatic bradycardias.
CONTRAINDICATIONS Phaeochromocytoma / atrial and ventricular tachyarrythmias / cyclopropane and

halogenated hydrocarbon anaesthetics / hyperthyroidism / ergotamine.
SPECIAL PRECAUTIONS Patients on MAOIs or tricyclics need decreased starting dose.

Hypovolaemia should be corrected.
Peripheral vascular disease / cardiac ischaemia.
INTERACTIONS Myocardium sensitised by halogenated anaesthetics.

MAOIs and tricyclics potentiate cardiac effects. Alpha and beta blockers decrease effects.
Concurrent I V phenytoin gives hypotension.
Ergotamine,methylsergide give enhanced vasoconstriction.
Digitalis can produce cardiac arrythmias.
ADVERSE EFFECTS Ectopic beats / tachycardia / anginal pain / palpitations / hypotension / vasoconstriction /
nausea / vomiting / headache / dyspnoea /
DOSING / ADMINISTRATION I V infusion 2 - 5 mcg / kg / min = “renal dose”.

5 - 10 mcg / kg / min = “cardiac dose”
TOXICOLOGY Excessive increase in BP / tachyarrythmias. ---slow or stop infusion.
WITHDRAWAL SYNDROMES Usually “wean” from infusion.
34
Doxycycline
HISTORY Prototype broad spectrum antibiotic.
STRUCTURE/CLASS Tetracycline group of antibiotics -- bacteriostatic.
PHARMACODYNAMICS Bind to 30s subunit of bacterial ribosome to inhibit protein synthesis.

Selective inhibition --- mammalian cells fail to concentrate tetracyclines.
ABSORPTION 90 - 100% absorbed in gut -- mainly in upper small intestine.

Best in absence of food.
Absorption is impaired by chelation with divalent cations -- Al 3+.
DISTRIBUTION Widely distributed to tissues and fluids except CSF.

40 - 80% protein bound.
METABOLISM Concentrated by the liver in the bile.
EXCRETION Excreted mainly in urine and faeces ay high concentrations and in biologically inactive forms.
INDICATIONS Infections with mycoplasma pneumoniae, chlamydia , gonorrhoea, rickettsia, spirochetes,

mixed bacterial respiratory infection.
Also ; acne vulgaris, UTI, Lyme disease, leptospirosis.
CONTRAINDICATIONS 1 Pregnancy.
2 Hypersensitivity to tetracyclines.
3 Children up to 12-15 yrs. It chelates with Ca++ in bones and cartilage damaging bones and
teeth.
SPECIAL PRECAUTIONS Breast feeding.

Sunlight can cause a photosensitivity reaction.
INTERACTIONS Absoption impaired by antacids, colloidal bismuth, iron preparations, milk.

Depress plasma prothrombin activity therefore decrease oral anticoagulant dose.
May interfere with bacteriocidal action of penicillin.
ADVERSE EFFECTS Nausea / vomiting / diarrhoea / photosensitivity / enamel hypoplasia / tooth discolouration /
hypersensitivity reaction (rare) / bone marrow depression / oesophagitis (rare)
DOSING / ADMINISTRATION 200 mg PO on first day and then 100 mg daily.

Severe infections 100 mg bd.
TOXICOLOGY Any toxic effect from tetracyclines in overdose is usually due to hypersensitivity reactions and
should be treated as such.
35
Enoxaparin
HISTORY Derived from the intestinal mucosa of pigs
STRUCTURE/CLASS A low molecular weight heparin
PHARMACODYNAMICS Binds to and increases activity of AT-III → Inhibits factor Xa

Has less effect on thrombin (IIa) than unfractionated heparin (but efficacy is equal)
ABSORPTION Given SC and IV, (SC bioavailability 92%)
DISTRIBUTION 80% protein bound

Vd = 6L (little more than circulating plasma volume)
METABOLISM
EXCRETION Renally excreted
INDICATIONS DVT/PE (treatment and prophylaxis)

Acute coronary syndrome
Treatment of unstable angina, and MI
CONTRAINDICATIONS
SPECIAL PRECAUTIONS Heparin-induced thromcytopenia → Monitor platelets

Renal impairment
INTERACTIONS
ADVERSE EFFECTS Heparin-induced thromcytopenia

Bleeding
DOSING / ADMINISTRATION Adjust in renal impairment
TOXICOLOGY Incompletely inactivated by protamine
36
Erythromycin
HISTORY Produced by the growth of certain strains of streptomyces erythreus.
STRUCTURE/CLASS Macrolide antibiotic -- bacteriostatic and bacteriocidal depending on its concentration and the
type of organism.
PHARMACODYNAMICS Binds to the 50s subunit of the bacterial ribosome to inhibit protein synthesis.
Erythromycin binds only to the ribosomes of bacteria and not to the cytoplasnic ribosomes of
the host cells and therefore has low toxicity.
ABSORPTION Erythromycin base is destroyed by stomach acid therefore needs enteric coat.
Erythromycin stearate / ester is quite acid resistant and well absorbed P O .
DISTRIBUTION Distributed widely except to CSF.

Half life = 2-3 hrs in severe renal impairment half life = 4 - 7 hrs.
Vd = 40% of body weight.
METABOLISM Oral bioavailability is 35%.

In normal hepatic function erythromycin is concentrated in the liver and excreted in bile.
EXCRETION Only 5% of dose is excreted renally (unchanged)

Principle excretion is via the liver.
Also excreted in the faeces.
INDICATIONS Corynebacteria infection (diphtheria)

Respiratory / neonatal / ocular or genital chlamydia infections.
Pneumonias ( mycoplasma and legionella)
CONTRAINDICATIONS Known hypersensitivity to erythromycins.

Patients taking astemizole and terfenidine.

Lactation.
Hepatic dysfunction.
INTERACTIONS Inhibits cytochrome P450 therefore increases blood levels of theophylline / carbamazapine
cyclosporin / triazolam / astemizole. Increases bioavailability of digoxin by 10%.
With oral anticoagulants leads to increased prothrombin time.
May interact with terfenidine to prolong Q T interval.
May antagonise lincomycin.
ADVERSE EFFECTS Irritant to vessels.

Abdo pain / nausea / vomiting / diarrhoea.
Hypersensitivity reactions (<0.5%),ototoxicity, acute cholestatic hepatitis - all less common.
DOSING / ADMINISTRATION P O erythromycin base / stearate / estolate = 0.25 - 0.5 gm 6 hourly.
I V erythromycin lactobionate via I V continuous infusion / intermittent I V infusion up to 15 -
20 mg / kg / day. Most stable at pH 6.5-7.5. Inactivated at pH < 5.5.
TOXICOLOGY General supportive measures in patients with OD erythromycin -- generally LOW toxicity.
37
Ethanol
HISTORY Is a sedative hypnotic consumed as a social drug.
STRUCTURE/CLASS C2H5OH.
PHARMACODYNAMICS 1 Effects the membrane and enzyme Na+ / K Ca++ ATPase. Acetylcholine esterases etc.
2 Increases the number of GABA receptors and decreases glutamate receptors.
Decreases the action potential.
Decreases EPSP / IPSP.
ABSORPTION Rapidly and completely absorbed.

Peak level = 30 mins.
DISTRIBUTION Rapid distribution.

Vd = 0.7 L / kg
METABOLISM 90% oxidised in the liver. Rest in lungs and kidneys.

Zero order kinetics.
EXCRETION CO2 + H2O.
INDICATIONS Social drug.
CONTRAINDICATIONS
SPECIAL PRECAUTIONS With other CNS depressants.
INTERACTIONS 1 Phenothiazines, sedative hypnotics.

2Hepatic enzyme induction will influence some drugs.
3 Hypoglycaemic drugs.
4Vasodilators
ADVERSE EFFECTS Acute and chronic effects.

G I Tract / Liver / myocardium / CNS / peripheral nerves / blood.
DOSING / ADMINISTRATION
TOXICOLOGY Acute : sedation, tachycardia, G I irritation.

Chronic : Cirrhosis, hepatitis , anaemia, peripheral neuropathy.
WITHDRAWAL Agitation / anxiety / insomnia / disorientation / hallucinations / fits.

SYNDROMES
38
Fentanyl
HISTORY
STRUCTURE/CLASS Synthetic opioid related to phenyl piperidine.
PHARMACODYNAMICS Mu receptor agonist. 80% more potent than morphine with decreased respiratory depression
effect. Shorter duration.
Increased dose - muscular rigidity. Probably via dopaminergic .
ABSORPTION Transdermal / I M / I V .
DISTRIBUTION Vd = 4L / kg.
84% plasma bound.
METABOLISM Liver
EXCRETION Kidney.
INDICATIONS Analgesic action of short duration during anaesthesia, premedication,induction etc.

Post op analgesia / analgesia supplement during G A.
Anaesthetic induction.
CONTRAINDICATIONS Children < 2 yrs.

Asthma.
Myesthenia gravis.
Other contrindications for narcotics.
SPECIAL PRECAUTIONS Impairment of pulmonary function.

Kidney / liver disease.
INTERACTIONS CNS drugs.
ADVERSE EFFECTS Drug dependance / hypotension / respiratory depression / muscle rigidity / bradycardia.
DOSING / ADMINISTRATION 50-100 mcg IV .

Up to 750mcg as anaesthetic induction agent.
TOXICOLOGY Narcosis / muscular rigidity / CVS and respiratory depression
WITHDRAWAL SYNDROMES As other narcotics.
39
Flumazenil
HISTORY First introduced in 1987
STRUCTURE/CLASS Imidazobenzodiazepine derivative
PHARMACODYNAMICS Flumazenil competitively inhibits the activity at the benzodiazepine recognition site on the
GABA / benzodiazepine receptor complex
ABSORPTION Well-absorbed orally, but significant first-pass metabolism
Acts rapidly when given IV
DISTRIBUTION Widely distributed, crosses BBB into CNS
METABOLISM Rapid hepatic clearance → Short half-life (approx. 1h)
EXCRETION 95% urinary metabolites, 5% faeces
INDICATIONS Reversal of CNS effects in BZD overdose

Hastening recovery of BXD use in procedural sedation
CONTRAINDICATIONS Cautious use in known epileptic

If used in polypharmacy overdose including a TCA, seizures and arrhythmias may result
SPECIAL PRECAUTIONS Half-life is usually shorted than the benzodiazepine it is antagonising → Sedation commonly
recurs as it is eliminated → Repeat dosing may be required
INTERACTIONS
ADVERSE EFFECTS Agitation, confusion, dizziness, nauea

Can precipitate severe abstinence syndrome in physiologically dependent patients
DOSING / ADMINISTRATION 200 μg every 1–2 minutes until the effect is seen, to a maximum of 3 mg per hour
TOXICOLOGY
40
Fluoxetine
HISTORY First SSRI in USA. Developed to have less side effects than TCA.
STRUCTURE/CLASS Antidepressant.
Selective Serotonin Reuptake Inhibitor (SSRI).
Minimal autonomic toxicity therefore decreased CV side effects.
PHARMACODYNAMICS Blocks serotonin reuptake in CNS at nerve endings leading to antidepressant

serotonin deficiency.
Also blocks serotonin uptake into platelets.
ABSORPTION 95% absorbed orally.

Decreased absorption with food.
Tmax = 6-8hrs
DISTRIBUTION Vd = 20-45 L/kg therefore large distribution

94% protein bound.
METABOLISM Liver to norfluoxetine active metabolite / racemic mix 50/50 R and S both active -
enantromers.
Half life of fluoxetine 3/7 (53 hours) - prolonged therapy 5/7
Half life norfluoxetine 7/7
Steady state reached after 2-3/52. Norfluoxetine/ linear pharmacokinetics
EXCRETION 80% urine excretion
15% faeces/5/52
INDICATIONS 1. Major depression.

2. Bulimia nervosa.
3. Obsessive compulsive disorders.
4. PMT
CONTRAINDICATIONS Anxious elderly

MAOI
Pregnancy and lactation
SPECIAL PRECAUTIONS Stop if develop rash - severe vasculitis
INTERACTIONS MAOI - “serotonin syndrome” - hyperthermia / muscle rigidity / myoclonus

Additive effect on CNS depressive medications e.g. EtOH and barbiturates.
Increases other antidepressent and lithium levels when used in combination.
Affects protein bound medication.
ADVERSE EFFECTS Rash - vasculitus / allergic reaction / anxiety / insomnia/ dizziness / seizures /
emotional lability / headache/ weight loss / anorexia / nausea / diarrhoea /
abdominal pain/ pruritis/ palpitations / altered platelet function/ fatigue
DOSING / ADMINISTRATION Depression - 20mg PO increasing to 80mg PO daily max - full effect after 4/52
Bulimia - 60mg PO daily
O/Cdisorder - 20-60mg PO daily
TOXICOLOGY Agitation / hypomania / restlessness/ nausea and vomitting / increased reflexes.

Treatment - ABC / activated charchoal/ if seizures use diazepam.
Dialysis of no benefit
Tachycardias usually only atrial
41
Frusemide
HISTORY Developed as a sulphonamide derivative.
STRUCTURE/CLASS Loop diuretic.

Carboxyl group with sulfamoyl moiety on C5, halide or phenoxy group on C4 and substituted
amino group at C2 or C3.
PHARMACODYNAMICS Inhibits Na+ / K+ / 2 Cl- transport system in luminal membrane of ascending Loop of Henle.
Decrease absorption of NaCl and diminish normal lumen positive potential from K+ recycling.
Increase Mg++ and Ca++ excretion. Ca++ is reabsorbed therefore Frusemide does not cause
hypocalcaemia. Can however be useful in hypercalcaemia..
Increases blood flow through vascular beds.
ABSORPTION Rapidly absorbed from G I tract.

Absorption rates = 60 - 69% (health) 40 - 43% ( end stage renal failure)
Duration of effect = 2 hrs I V and 6-8 hrs oral.
DISTRIBUTION Extensively bound to plasma proteins (mainly albumin). 91 -99% bound in healthy people.
METABOLISM Frusemide glucuronide is the major bio-transformation product of Frusemide.
EXCRETION Normal renal function - approx 80% of I V or I M dose is excreted in urine.

65% after oral dose.
Rest in faeces.
INDICATIONS Oedema of CHF

Cirrhosis of the liver and renal disease including nephrotic syndrome and acute renal failure.
Hyperkalaemia Anion overdose.
CONTRAINDICATIONS Sensitivity to frusemide or sulphonamides.

Complete renal shutdown.
Severe hypokalaemia / hyponatraemia / hypovolaemia / hypotension.
Hepatic coma.
Neonatal jaundice.
SPECIAL PRECAUTIONS Strict Na intake not advisable.

Prostatic hypertrophy or problems with micturition.
Periodic checks on blood and urine.
High potassium diet.
INTERACTIONS Increase of ototoxicity with amonoglycosides and cisplatin.

Nephrotoxicity with aminoglycosides.
Addition of ACE inhibitor may cause profound hypotension.Hypokalaemia may precipitate
digitalis toxicity.
ADVERSE EFFECTS Electrolytes and water balance disturbances.

Symptoms of hypovolaemia.
Increases cholesterol and triglycerides (usually transient) Decreased serum calcium.
Occasionally - GI disorders
Worsening of diabetes.
Photosensitivity rashes.
DOSING / ADMINISTRATION Tablet = 40 mg / 250 mg. Oral solution = 10mg / ml Ampoules = 20 mg / ml.
Dose range 10 - 500mg daily.
TOXICOLOGY Dehydration / blood vol reduction / hypotension / electrolyte imbalance / hypokalaemia /

hypochloraemic alkalosis.
Treatment = replacement of fluids and electrolytes.
42
Gentamycin
HISTORY Originally obtained from Streptomyces species.
STRUCTURE/CLASS Aminoglycoside group of antibiotics -- bacteriocidal.

Has a hexose nucleus to which amino sugars are attached by glycosidic links.
PHARMACODYNAMICS Penetrate the bacterial cell envelope via partial active transport ( active transport = O2
dependant.
Bind to the 30s unit of the bacterial ribosome and inhibits protein synthesis by 1) interfering
with initiation complex of peptide formation. 2) inducing misreading of code on m RNA
template 3) causing polysome breakup.
ABSORPTION Poorly or not absorbed from the intact G I tract, virtually all the oral dose is excreted in faeces.
Well absorbed post parenteral injection.
10% protein bound in plasma.
DISTRIBUTION Highly polar - doesn’t enter cells readily.

Largely excluded from CNS and eye.
Half life = 2-3 hrs. Vd = 18L / 70 kg
METABOLISM No significant metabolic breakdown occurs by host mechanisms.
EXCRETION Mainly by glomerular filtration in the kidney (90%)
INDICATIONS Effective against gm-ve and +ve bacteria. Used in systemic gm -ve infections esp
pyelonephritis. used also in endocarditis with faecal strep / gm -ve bacteria ie. E Coli,
Pseudomonas.
Resp tract infection / infected wounds / bone and soft tissue infection.
CONTRAINDICATIONS Pregnancy.
Previous toxic reactions to aminoglycoside therapy.
SPECIAL PRECAUTIONS Renal impairment.
INTERACTIONS Works synergistically with penicillins --penicillin damages the cell wall so gentamycin can get
to ribosomes.
toxic effects increase when combined with loop diuretics, vancomycin and cyclosporin.
Prolongs the effects of neuromuscular blocking drugs.
ADVERSE EFFECTS Vestibular damage (high doses and in presence of renal impairment)
Nephrotoxicity <2% incidence.
Allergy ( not common)
DOSING / ADMINISTRATION I V / I M - 80mg 8 hourly or 3-5 mg / kg / day as once daily dose if creatinine clearance is
established.
Topical preps = eye drops and creams for infected burns
TOXICOLOGY In OD as drug is almost entirely eliminated by the kidney fluid loading may hasten its
excretion.
Dialysis will also aid in drug removal.
WITHDRAWAL
SYNDROMES
43
Glyceryl trinitrate
HISTORY Synthesized in 1846. Introduced 1879.
STRUCTURE/CLASS Nitrate = R-C-O-NO2 = Polyol ester nitric acid

Nitrite = R-C-O-NO = polyol ester nitrous acid
PHARMACODYNAMICS Denitrated in smooth muscle cells (not cardiac or skeletal muscle) by glutathione - S-
transferase to NO2 ? to NO.
NB: diffuses across cell membrane. Activates guanylal cyclase causing increased cGMP leading
to decreased platelet aggregation and smooth muscle relaxation.
ABSORPTION Lipid soluble - topically mucous membranes - sub lingual, buccal.

10-20% oral bioavailability secondary to first pass effect.
DISTRIBUTION GTN half life 2-8mins.

Dinitroglycerin metabolites halflife = 2-3 hrs
METABOLISM Hepatic - organic nitrate reductase produce 2 dinitroglycerins (also vasodilators) and 2
mononitros
EXCRETION Excreted via kidney.

Glucuronide conjugates of denitrated metabolites.
INDICATIONS 1. Angina of effort - decreases preload > decreases afterload.

2, Variant angina (vasospastic).
3. Unstable angina ?also related to platelet effect.
Effect is to decrease myocardial VO2 primarily by decreasing intraventricular pressure
(Laplace relationship - decreased ventricular wall stress by decreasing intraventricular
pressure/ volume)
In coronary artery spasm the effect is to relieve spasm (dilatation).
CONTRAINDICATIONS
SPECIAL PRECAUTIONS Tablet - volatile - adsorbs to plastic surfaces

Not light sensitive.
Tolerance (tachyphylaxis) therefore nitrate free interval required.
INTERACTIONS
ADVERSE EFFECTS 1. Hypotension

2. Reflex response to vasodilatation may increase myocardial VO2.
3. Coronary steal phenomenon
4. Headache
DOSING / ADMINISTRATION Sublingual - spray / tablet (0.4-0.6mg) Oral (increase dose)
Topically - patch/ointment Nitrites (inhalational - amyl nitrite)
IVI (5-100mcg/min)
TOXICOLOGY Overuse / overmedication / lack of nitrate free interval.
Occupational exposure can lead to withdrawal vasospasm and subsequent angina / MI.
WITHDRAWAL
SYNDROMES
44
Haloperidol
HISTORY Haloperidol is an older, typical antipsychotic, developed in 1958 in Belgium.
STRUCTURE/CLASS Butyrophenone antipsychotic
PHARMACODYNAMICS Action at dopaminergic system in CNS. Receptor blocker. D2 stereoselectively.

D2 > D1 = D4 > alpha 1 > 5HT2. Dopamine antagonist.
1. Mesolimbic - mesocortical blocking of D2 receptor causes antipsychotic effect.
2. Nigrostriatal - blocks D1 receptor causes Parkinsonism.
3. Tuberoinfundibular blocking of D2 causing loss of inhibition and prolactin
secretion.
4. Medullary periventricular causes changes in eating.
Alpha 1 blocker therefore orthostatic hypotension.
ABSORPTION Well orally. 60% bioavailability. First pass effect.

T max = 10 min T max oral = 4-6 hrs.
Half-life = 12 -40 hrs.
DISTRIBUTION 92% protein bound. Lipophilic Accumulates in fat and present for weeks.
Vd = 18L / kg.
METABOLISM Liver via dealkylation.

Oxidation and conjunction of inactive metabolites.
EXCRETION Urine - mostly inactive metabolites.

Faeces via bile
INDICATIONS Psychosis ; schizophrenia ; schizoaffective disorder.

Mania: hyperactive psychotic states
Tourette’s syndrome
Intractable hiccups.
CONTRAINDICATIONS CNS depression : e.g. coma, ETOH

Depressive states: epilepsy, Parkinson’s
SPECIAL PRECAUTIONS Elderly - over-sedation.

CVS disease - causes transient hypotension
Anginal pain
Thyrotoxicosis
Liver dysfunction
INTERACTIONS Potentiates CNS depressants. Decreases effect of Levodopa. Adrenalin antagonist.

Decreases tricyclic metabolism, therefore increases effect.
Interferes with warfarin
Encephalopathic syndrome with Lithium
ADVERSE EFFECTS Extrapyramidal / Parkinson-like / akathisia / dystonic reaction / anxiety / EEG

changes causing seizures / tardive dyskinesia / dystonia / tachycardia / prolonged
QT / orthostatic hypotension / ventricular arrhythmia / hyperolactinaemia / rash /
photosensitivity / retinopathy / cataracts / decreased ejaculation /
IRREVERSIBLE: neuroleptic malignant syndrome
DOSING / ADMINISTRATION Oral - 0.5-5 mg, 2-3 x / day. Max. 200mg/day

IM - 2-5 mg 4-8 hourly
Hiccups: 0.3mg TID
Children: 0.025mg/kg/d in divided doses
TOXICOLOGY Respiratory depression / hypotension / arrhythmia / sedation / extrapyramidal
reaction
Supportive treatment - ventilate / fluids / anti-Parkinson meds. Monitor
AVOID ADRENALINE
45
Halothane
HISTORY Introduced in 1956 - major development as non-inflammable and non-explosive. Was much
more potent and less irritant with moderately rapid induction and recovery. Also less toxic
than previous agents.
STRUCTURE/CLASS Inhalational general anaesthetic
PHARMACODYNAMICS Mechanism unclear -- probably 1 ) increased threshold for firing at cellular level therefore
decreasing neuronal activity. 2) ? modify ionic currents
CVS: decreases blood pressure and pulse / RS: depressant / decreases, TV increases RR / CNS:
increased ICP ( increased cerebral vasodilation) / kidneys: decreased GFR / liver: decreased
hepatic blood flow / uterus: relaxant.
ABSORPTION Thru alveoli into the blood stream and thence into the brain and other tissues
Absorption and distribution depend on: 1) solubility of agent 2) its concentration in inspired
air 3) pulmonary ventilatory rate 4) pulmonary blood flow 5) the concentration gradient
between arterial and mixed venous blood
Moderate to high solubility.
DISTRIBUTION Slower induction

Slower recovery
METABOLISM 15 to 20% of inspired Halothane is metabolised:

1) oxidative metabolism leads to formation of trifluoroaceticacid and release of Bromide and
Chloride ions
2) at low p02 produces chlorotriflurorethyl free radicals ( this reacts hepatic membrane)
EXCRETION Lungs: Major route

Liver: Metabolism by enzymes into break-down products
INDICATIONS As inhalational induction / maintenance agent for GA s
CONTRAINDICATIONS 1) liver damage

2) previous “halothane hepatitis”
3) repeat exposure within 3 months
SPECIAL PRECAUTIONS 1) good ventilation needed

2) neurosurgery ( need hyperventilation to couteract the increased CSF pressure with
Halothane )
3) malignant hyperpyrexia
4) nil dangerous tasks for 24 hours after GA
INTERACTIONS Augments non-depolarizing muscle relaxants
Adrenaline / Aminophylline / Theophylline --- may cause arrythmias if used concurrently
ADVERSE EFFECTS 1) Increased ICP - from cerebral vasodilatation / 2) decreased blood pressure and PR
3) arrythmias / 4) Halothane hepatitis / 5) decreased tidal volume, increased RR, resp.
depressant / 6) malignant hyperpyrexia
DOSING / ADMINISTRATION Mask anaesthetic
MAC = 0.75 ( need 0.5 to 1.5 MAC)
MAC decreased with elderly or adjuvant drugs eg opiods and benzodiazepines
TOXICOLOGY Nil antidote.
Treatment: maintain respiratory function / airway support / 02
maintain cardiovascular function
treat internal ingestion symptomatically
46
Heparin
HISTORY
STRUCTURE/CLASS A heterogeneous mixture of sulphated mucopolysaccharides
PHARMACODYNAMICS Reversibly binds to Antithrombin-III → Accelerates binding of AT with factors IIa, IXa, Xa
ABSORPTION No data on oral bioavailability. IV and SC bioavailability appears to be the same
DISTRIBUTION ⅓ bound to AT-III, the rest to albumin, fibrinogen, proteases

 Low Vd
 Apparently does not cross the placenta (can be cautiously used in pregnancy)
METABOLISM Liver, kidneys, and RES
EXCRETION Urine
INDICATIONS 1. Prevention of venous thromboembolic disease

2. Priming of haemodialysis, CP bypass
3. DIC
4. Fat embolism
CONTRAINDICATIONS
SPECIAL PRECAUTIONS Platelet counts should be performed frequently

Thrombocytopenia should be considered to be heparin-induced
New thrombus can be the result of HIT
INTERACTIONS
ADVERSE EFFECTS Excessive bleeding

Heparin-induced thrombocytopaenia
TOXICOLOGY
47
Hepatitis B Vaccine
HISTORY
STRUCTURE/CLASS Injection of hepatitis B surface antigen inactivated (recombinant)

0.5mg aluminium (as hydroxide). Thiomersal
Purified and inactive virus coat protein
PHARMACODYNAMICS
ABSORPTION
DISTRIBUTION Greater than 90% protective
METABOLISM
EXCRETION
INDICATIONS Exposure to Hepatitis B or possible exposure

Double dose for immunocompromised patients
CONTRAINDICATIONS Sensitivity to components of injection

Acute severe febrile illness
SPECIAL PRECAUTIONS If other vaccinations necessary must be given with different syringes at different sites
Do not inject into gluteal muscle
INTERACTIONS Not likely to interact with other inactivated vaccines
ADVERSE EFFECTS Well tolerated

Can get local site soreness, erythema or swelling
DOSING / ADMINISTRATION Give I M. Three doses

One initially, one at one month, one at six months
TOXICOLOGY Nil known
WITHDRAWAL
SYNDROMES
48
Indomethacin
HISTORY Introduced in 1963 after search for compounds less irritating to gastric mucosa than
salicylates.
STRUCTURE/CLASS Indole derivitive. Highly effective NSAID (?most potent) with marked analgeisic, antipyretic
and anti-inflammatory properties.
PHARMACODYNAMICS Potent inhibitor of PG synthesis. Also inhibits production of Tx and PG via reversible inhibition
of cyclooxygenace - relief of pain, inflammation.
Decreased sensitivity of vessels to bradykinin and histamine, decreased lymphokine
production by Tcells.
ABSORPTION Well absorbed. PO - peak concentration = 2 hrs.

Steady state level only 1.4x single dose concentration therefore no loading dose required.
90% abosrbed after 4hrs (12hrs for SR form).
PR more quickly absorbed (< 1hr to peak) but less extensive (80-90%).
IM peak levels = 1hr - 100% bioavailable.
DISTRIBUTION Vd = 18L / 70kg. Protein binding 90%. 100% oral bioavailability.
METABOLISM Clearance 8.4L/70kg/hr. Half life = 4-5 hrs.

Mainly hepatic to desemthyl, desbenzoyl, desmethyl-desbenzoyl derivitives - all unconjugated.
EXCRETION Both unchanged drug and active metabolites excreted in urine and bile, with an appreciable
enterohepatic circulation. Total urinary excretion 60% (26% of this indomethacin +
glucuronide = 15-16%of total, rest as metab.) 33% biliary (1.5% as Ind).
INDICATIONS Acute gout/ arthritis/ acute bursitis/ tendinitis/ synovitis/ sprains, strains/ low back pain/
fever/ renal colic
CONTRAINDICATIONS Pregnancy/ lactation/ allergy/ asthma/ urticaria/ history of recurrent GI ulceration.
SPECIAL PRECAUTIONS Past history peptic ulcer disease/ nasal polyps/ angioedema, asthma/ elderly/ decreased
renal function, coagulation defects/ anticoagulant treatment/ infection.
INTERACTIONS Increased Li plasma levels (secondary to inhibition of renal PG synthesis --- decreased RBF) /
increased MTX toxicity / increased bleeding risk with anticoagulants/ asprin significantly
increases ADRs especially GI bleed.
ADVERSE EFFECTS GI frequent - dose related, reduced if taken after food, antacid, milk.
Abdo pain/ epigastric distress/ nausea/ vomitting/ diarrhoea/ single or multiple ulcerations
of oesophagus, stomach, duodenum, small and large bowel/ stomatitis/ gastritis/ flatulence.
DOSING / ADMINISTRATION Oral : 25, 50mg capsules. 70mg SR. Suppository 100mg. Injection 100mg/3mls.
Gout - 150-200mg/d divided, OA/RA = 100mg nocte. Dysmenorrhoea = 75mg/day.
TOXICOLOGY OD- nausea & vomitting/ intense headache/ diziness/ confusion/ disorientation/lethargy/
parasthesias/ numbness/ convulsions.
Treatment : symptomatic and supportive/charcoal.
Observe several days because of risks of GI ulceration. Antacids may be helpful.
WITHDRAWAL Reversal of interactions above, rebound antihypertensive effect on betablockers.

SYNDROMES
49
Insulin
HISTORY
STRUCTURE/CLASS Endocrine pancreatic hormone from beta cells = 75% of islet mass, along with C-peptide, pro-
insulin, isletamyloid polypeptide.
Pro-insulin produced as 86 amino acid single chain molecule, hydrolized to insulin plus C-
peptide by removal of two amino acids at each end of C-peptide.
PHARMACODYNAMICS Secretion stimulated by glucose/ mannose/leucine/arginine/sulphonylureas/ vagal

stimulation.
Inhibited by alpha-adrenergic stimulation/somatostatin / diazoxide / phenytoin / colchicine
Acts to stimulate storage of glycogen/protein from circulating substrates.
Affects glucose transporters/liver- stimulates VLDL, glycogen synthesis and inhibits
glycogenolysis, gluconeogenesis, protein catabolism and urea production.
ABSORPTION Regular = short acting / crystalline. SC gives effect after 15 mins lasts for 5-7 hrs duration.
Medium semilente = amorphous - relatively rapid onset usually 30% with ultralente - lente.
DISTRIBUTION Once in circulation is bound by receptors found in most tissues,but significant biological
response only in muscle , liver, fat. Binds with high specificity and affinity. Also binds to
brain, placenta, heart, RBC, pancreas, kidney, gut (tissues with glucose transporters). Half life
(alpha) = 3-5mins.
METABOLISM Liver, kidney (glutathione transhydrogenase) --hydrolysis/reduction of S2 bonds. Further

degredation by proteolysis. Endogenous insulin 60% hepatic (significant first pass effect).
30-40% renal. Exogenous insulin 30-40% hepatic, up to 60% renal.
EXCRETION ? mostly reprocessed, a little excreted as smaller peptides.
INDICATIONS IDDM / gestational diabetes / NIDDM -not adequately controlled by weight loss, exercise,diet.
Control necessary to prevent acute and chronic complications of diabetes.
CONTRAINDICATIONS Hypoglycemia.
Stress hyperglycemia.
Iatrogenic hyperglycemia in non-diabetics.
SPECIAL PRECAUTIONS Tight control avoided (a) those with advanced renal disease (decreased renal metabolism of
insulin).Also elderly as risks of hypoglycemia outweigh benefits of tight control; (b) < 7 years
of age because of extreme succeptability to brain damage from decreased glucose and no
evidence that tight control essential
INTERACTIONS Alcohol: Acute intake can increased hypoglycemic effects of insulin (especially in fasted
patients) by decreasing substrates for gluconeogenesis. Chronic heavy use of alcohol can
cause chronic pancreatitis and worsen diabetes.
Betablockers: Inhibit recovery from hypoglycemia by inhibiting glycogenolysis and lipolysis.
Secretion: Inhibited by many drugs. Diureticsmay increase or decrease insulin required.
ADVERSE EFFECTS Hypo: secondary to delayed meal, over-exertion, too much insulin, not monitoring Bms. Signs
= confusion, odd behaviour, coma, autonomic hyperactivity, nausea, increased heart rate,
palpitations, sweating, tremor, faintness and dizziness.
DOSING / ADMINISTRATION Routes: SCinj / intranasal (as detergent) / pens / CAPD bags/ IV / intraperitoneal pumps
Acute: Closed loop systems or IV with sliding scale for DKA & peri-operative glucose control.
TOXICOLOGY OD = intentional, iatrogenic or secondary to unintentional OD, missed meal, D&V, excessive
exercise, infection, alcohol.
Symptoms = hunger,nervousness, warmth, sweating, palpitations, fatigue, confusion,
drowsiness, headache, anxiety, blurred vision, diplopia, numbness off lips, nose, fingers, coma,
death.
Treatment = Soluble CHO, juice, food, IV dextrose, IM glucagon.
WITHDRAWAL Hyperglycemia.
SYNDROMES Effects of diabetes.
50
Ipratropium
HISTORY
STRUCTURE/CLASS Anticholinergic bronchodilator

Quaternary isopropyl derivative of atropine.
PHARMACODYNAMICS Blocks the action of acetylcholine at parasympathetic sites in bronchial smooth muscle
causing bronchial dilation
Onset of ;bronchial dillation 1-3 minutes after administration
Peak effect in 1.5 to 2 hours
Duration 4-6 hours
ABSORPTION Not readily absorbed into the systemic circulation from the surface of the lung or GI tract
<1% absorbed
DISTRIBUTION Inhalation : 10-15% of dose reaches lower airways

Approximately 90% of the dose is swallowed
Half life = 3 hours
METABOLISM
EXCRETION Approximately 90% excreted unchanged in faeces
INDICATIONS Broncho spasm associated with COPD, bronchitis and emphysema
CONTRAINDICATIONS Hypersensitivity to atropine or its derivatives
SPECIAL PRECAUTIONS Not indicated for initial treatment of bronchospasm as a sole agent.
Caution with narrow angle glaucoma
Prostatic hypertrophy
Bladder neck obstruction
INTERACTIONS Salbutamol - increased effect of both drugs

Increased toxicity with anticholinergics
ADVERSE EFFECTS Poorly absorbed from lung so systemic effects are rare
CNS / nervousness, dizziness, fatigue, headache
DOSING / ADMINISTRATION Nebuliser solution 0.025% solution use 1 - 2 mls 2 - 4 hourly.

Metered dose inhaler. Adults 2 puffs qid. Children 1-2 puffs tid.
TOXICOLOGY Dry mouth, drying of secretions, cough,nausea, GI distress, blurred vision
If life threatening treat with physostigmine 1-2mg SC or IV
WITHDRAWAL
SYNDROMES
51
Lignocaine
HISTOR Cocaine 1860
Procaine 1905
Lignocaine 1943 synthesized by Lofgren
STRUCTURE/CLASS Amide local anaesthetic

Class IB antiarrythmic
Less potent than Bupivicaine Amide - aromatic ring - ionizable group
PHARMACODYNAMICS Blocks Na+ channels - both activated and inactivated channels

Time & voltage dependant
more negative (less affinity for LA)
Increases speed of conduction (less affinity)
ABSORPTION Oral x 3% bioavailability

IV
SC
Epidural /spinal
DISTRIBUTION Vd - wide - sequestered in fat
METABOLISM Dealkyated in liver by mixed oxidases

T½ 2 hrs (IV)
EXCRETION Urine
INDICATIONS 1. VT/VF after cardioversion - (IV) - controversial (?MI --> standstill)

2. LA --> production of LA
Regional / epidural
CONTRAINDICATIONS In severe liver disease (IV dose change)

Allergy
Severe hypotension
SPECIAL PRECAUTIONS CNS - seizures in toxic dose

CVS --> hypotension
AMI --> cardiac standstill 1%
INTERACTIONS With digoxin

With cimetidine - decreased liver flow
With propanolol - decreased liver flow
ADVERSE EFFECTS 1. Hypotension - secondary to suppressed myocardium. Arrest. Bradycardia

2. Headaches, dizziness
3. Seizures
DOSING/ADMINISTRATION N.B. 1% solution = 10mg/ml

IV 1-2mg load 1-2mg/kg infusion
Local 1% 20-40ml
Max 2mg/kg IV, 3mg/kg local or 5mg/kg with adrenaline.
TOXICOLOGY Seizures + + CVS hypotension Arrythmia
WITHDRAWAL
SYNDROMES
52
Lithium
HISTORY Discovered in 1949
STRUCTURE/CLASS Small monovalent cation. “Mood stablizing agent”

(or “anti-manic”)
PHARMACODYNAMICS Substitutes for Na+ in generating action potential and slows Na+ / Na+ exchange. May
enhance some actions of serotonin and decrease noradrenaline and dopamine turnover.
Decreases levels of PIP2 (and therefore IP3 and DAG).
Blocks noradrenaline sensitive adenylylcyclase.
ABSORPTION Complete in 6-8 hrs.

Peak plasma levels in 30 mins to 2 hrs.
DISTRIBUTION In total body water. Slow entry to intracellular compartment.

Initial Vd = 0.5L/kg - increases to 0.9 L/kg.
No protein binding.
METABOLISM None
EXCRETION Entirely in urine. Clearance = 20% of creatinine.

‘Plasma half life = 20 hrs.
INDICATIONS Mania and hypomania.

‘Treatment of bipolar affective disorder.
Control of aggressive or self-mutilating behaviour.
CONTRAINDICATIONS Renal insufficiency.

Cardiovascular insufficiency
Addisons disease
Untreated hypothyroidismj.

Elderly
INTERACTIONS Clearance decreased by diuretics and some NSAIDs

May get more severe extrapyramidal reactions with neuroleptics.
ADVERSE EFFECTS Tremor, / hyperactivity/ ataxia/ altered thyroid function/ goitre / polydipsia/ polyuria/
nephrogenic DI / sick sinus / oedema
DOSING / ADMINISTRATION Daily dose of 0.5meq / kg (300mg = 8 meq of lithium)

Give in divided dose . Levels after one week.
TOXICOLOGY Anorexia / vomitting / drowsiness / tinnitus.
At levels of 2-3 mmol / L get polyuria and seizures. Treat with dialysis.
WITHDRAWAL
SYNDROMES
53
Magnesium
HISTORY
STRUCTURE/CLASS Element essential for activity of many enzymes and normal function of nervous and
cardiovascular systems
PHARMACODYNAMICS Mechanism unclear but it influences Na+ / K+ / ATPase channel, K+ channel and Ca ++
channel
Bronchodilator
Decreases conduction time of the pacemaker.
Decreases CNS activity
Decreases NM transmission - anticonvulsant
ABSORPTION Oral 30%

IV full absorption, immediate onset of action
DISTRIBUTION 50% bone

45% cells
5% ECF
METABOLISM
EXCRETION Filtered ion excreted in kidney
INDICATIONS Arrythmias especially digitalis induced, Torsade, hypothermia.

Pre-eclamptic seizure
Asthma
Contoversial in post AMI prophylaxis
CONTRAINDICATIONS Renal failure

AV block
SPECIAL PRECAUTIONS Monitor Ca /phosphate

Myocardial damage
INTERACTIONS CNS depressants

N M blockers
Cardiac glycosides
ADVERSE EFFECTS Muscle weakness

Hypotension
Flushing
DOSING / ADMINISTRATION Oral dietary requirement 27 -54mg 3-4x / day

IV dose 2 - 5 g
TOXICOLOGY Large dose - leads to decreased respiration and CNS causing cardiac arrest
WITHDRAWAL
SYNDROMES
54
Marijuana
HISTORY Use recorded for thousands of years, known to Greeks. Since 1960s large rise of use in USA.
30-40 million have used it
Obtained from flowering tops of hemp plants
STRUCTURE/CLASS Active cannabinol is D9TH C(tetrahydrocannabinol)

Very lipid soluble
Most plants have a THC content of 1-2%
PHARMACODYNAMICS Mechanism is unknown. It is felt to be a highly selective receptor. Binding sites are mainly in
brain and receptors are G protein coupled. Early stage (2-3 inhalations) = “high” - euphoria,
uncontrollable laughter, altered time sense and sharpened vision. Later - relaxation,
drowsiness, decreased concentration, decreased balance and stance stability, pulse rate,
increased conjunctiva redenning.
High dose - hallucinations, delusions, paranoid feelings. Rarely a toxic psychosis. May cause
acute exacerbation in stabilized schizophrenics
ABSORPTION Depends of efficiency of smoking. Up to 50% absorbed from a cigarette

GIT absorption is complete, but THC is three times more potent when smoked compared with
PO
Plasma levels peak 10-30 minutes. Effects last 2-3 hours
DISTRIBUTION Large Vd
Receptors throughout CNS
Sequestered in lipid compartments of the body.
Metabolites are excreted up to a week after a single dose
METABOLISM Extensively metabolised - active metabolites and then more polar, inactive metabolites
No accumulation occurs ? Hepatic metabolism
EXCRETION Urine and faeces

Bile - may be resorbed
Found in urine for days/weeks
INDICATIONS None at present. May be used in the future for glaucoma, reduction of nausea / vomiting with
chemotherapy, anticonvulsant
CONTRAINDICATIONS Schizophrenia - may exacerbate psychosis
SPECIAL PRECAUTIONS All studies show impairment of higher tasks - eg driving, multistep tasks
INTERACTIONS Effects of alcohol in CNS depression are additive

Liver enzyme induction in chronic use will also increase metabolism of barbiturates and
alcohol
ADVERSE EFFECTS High enough doses cause depersonalization, panic attacks, tachycardias.
Frank toxic psychosis may occur acutely or after months of use
Chronic use - unexplained increase in plasma volume
DOSING / ADMINISTRATION One cigarette, equivalent to oral dose of 20mg D9TH C

Amount reaching blood is highly dependant on smoking technique and the amount destroyed
by pyrolysis.
TOXICOLOGY Brain damage has not been confirmed in humans, some suggestion of ultrastructural damage
being found in animals.
Concerns re effect on developing personalities
WITHDRAWAL Tolerance does develop to CNS effects, abrupt discontinuation after chronic use causes
SYNDROMES irritability, restlessness, nervousness, weight loss, insomnia
Increase in REM sleep , tremor.
Increase in body temperature lasts up to five days
55
Metoclopramide
STRUCTURE/CLASS Dopamine antognist antiemetic with cholinomimetic properties
PHARMACODYNAMICS Mechanism of action 1. inhibits central dopamine receptors - raises threshold of

chemoreceptor trigger zone reducing
reducing reaction of the adjacent vomiting centre.
2. promotes normal gastric emptying (stimulates upper GI motility)
3. decreases sensitivity of the visceral afferent nerves to the vomiting
centre
ABSORPTION PO - marked variability (individual differences in first pass metabolism)

Onset of action 1-3 mins (IV) 10-15 min (IM) 30-60 min (PO) effect 1-2 hours
DISTRIBUTION Plasma protein binding 13-22%
METABOLISM 50% conjugated in liver - glucuronide plus sulphates
EXCRETION 80% excreted in urine in the first 24 hours - 50% conjugated - 50% unchanged
elimination half life = 2.5 - 5 hours
INDICATIONS Nausea and vomiting

digestive disorders
migraine
CONTRAINDICATIONS When stimulation of GI motility dangerous - GI haemorrhage / obstruction / perforation

Phaeochromocytoma - release of tumour catecholamines
Hypersensitivity
SPECIAL PRECAUTIONS Tardive dyskinesia with prolonged treatment

Pregnancy - no clinical teratogenic effects - but not advised during first trimester
Persistent vomiting - need to assess and exclude cerebral irritation
INTERACTIONS Anticholinergics antagonise GI effects

Care with extrapyramidal effects with concommitant phenothiazine use.
May affect absorption of oral medications.
ADVERSE EFFECTS Extrapyramidal side effects - especially dystonic reactions in children and young adults Rx
benztropine
Incidence higher if daily dose higher than 0.5mg / kg
Onset within 36 hrs of treatment and resolve 24 hrs after withdrawal
DOSING/ADMINISTRATION IM / IV / PR / PO not exceed 0.5mg / kg / day. Young adults 30-60 kgs - 5mg tds
Adults 10mg tds dec. dose for children 1 - 2.5mg tds.
Young adults > 60 kgs 10 mgs tds.
TOXICOLOGY Supportive treatment

Treat dystonic reactions
WITHDRAWAL
SYNDROME
56
Midazolam
HISTORY
STRUCTURE/CLASS 1, 4 benzodiazepine/ sedative hypnotic

2 benzene rings joined by ring containing 2 nitrogens (diazo) 7 member diazo ring gives
sedative/hypnotic properties
PHARMACODYNAMICS Binds to gamma 2 subunit (probably benzo receptor) on area of alpha unit on GABA receptor
which increases chloride channel conductance.
Increased efficiency of GABAergic synaptic inhibition by decreased firing rate of neurones and
increased frequency of channel opening events.
Does not directly initiate chloride current only facilitates .
GABA receptor alpha, beta, gamma units. Major neurotransmitter inhibitor.
CVS decreases BP and increases HR in large doses.
Resp: decreases alveolar ventilation depressing medullary centre.
ABSORPTION Well absorbed orally - H2O soluble becomes lipid soluble at physiological pH → Crosses BBB
Tmax 15-30 mins
PR 50%
DISTRIBUTION Vd = 50L
Two stages. Distribution phase 10mins. Elimination phase 1 - 2.5 hrs.
96-98% protein bound. Half life = 2-4 hrs.
METABOLISM Liver - rapid and complete microsomal oxidation (phase1) to alpha-hydroxymidazolam.

Metabolites undergo conjugation (phase 2) with glucuronic acid eliminated as glucuronides in
kidney.
EXCRETION Urine 50-70% as metabolite.
INDICATIONS 1. Hypnosis
2. Sedation in pre-meds (PR in children)
3. Anaesthesia - Induction and maintenance
 Anterograde amnesia (75%) given 15-60 minutes before anaesthetic induction
4. Intraoperative sedation
5. Muscle relaxation
6. Long term sedation in ICU
7. Being used more as an anticonvulsant, as evidence of efficacy improves
CONTRAINDICATIONS Insomnia in psychotics.

SPECIAL PRECAUTIONS 1. Severe resp insufficiency.

2. Myasthenia gravis
3. Organic brain damage.
4. Dependence.
INTERACTIONS 1. CNS / sedative meds. - EtOH is potentiated / opiates/ phenothiazines

2. Increased plasma levels of erythromycin
3. Enzyme inducers/ drugs affecting liver met e.g. cimetidine decreased metabolism.
ADVERSE EFFECTS Sedative side effects which are dose dependent / physiological dependance / habituation
Slight decrease BP and increase PR
Amnestic episodes. Hypersensitivity. Paradoxical reaction aggitation/excitation.
DOSING / ADMINISTRATION Hypnosis oral 7.5 -10mg nocte for 4hrs sleep. ‘
Pre-med 15mg PO 30-60 minutes before theatre
Anaesthetic induction 10-15mg IV at 5mg/min.
Muscle relaxant 0.1-0.2 mg/kg IV/I M . Intranasal sedation : children
TOXICOLOGY Dizziness / fatigue/ ataxia / amnesia / blurred vision / respiratory depression .

Treatment - supportive . Charcoal Flumazenil 0.2 mg slow IV repeat every 60 secs. til patient
recovered. Infusion 0.1-0.4 mg / hr IV.
Fatal if OD with EtOH - CVS and respiratory depression.
WITHDRAWAL Variable onset hours to weeks. Spectrum - restlessness / tremor / anxiety / insomnia /
SYNDROMES inability to concentrate / muscuclar and abdominal spasms / delirium and convulsions.
Avoid abrupt discontinuation. Change to long acting dosage, decreasing slowly over months.
57
Morphine
HISTORY Extraction from poppy seeds. Use of Plant for 6,000 years. Active alkaloid isolated 1803 by
Serturner, German Pharmacist. Morpheus - Greek god of dreams.
STRUCTURE/CLASS Natural alkaloids Classes: Phenylanthrenes morphine / codeine

Semi synthetic alkaloids Phenylheptylamines methadone
Synthetic surrogates Phenylpiperidines pethidine / fentanyl
Benzomorphans pentazocine
PHARMACODYNAMICS Mechanism of action: Block mu, delta and kappa receptors. Mu and delta are supraspinal,
Mu, delta and kappa spinal anaesthesia.
Receptor action: via 1. Hyperpolarise post synaptic neurons (inc. K+efflux) Dec. Ca 2+ influx
in presynaptic nerves.
Effect via G proteins and cAMP.
Receptor distribution: Brain primary site - thalamus - midbrain - hypothalamus.
Dorsal horn spinal cord
Peripheral receptors e.g. pain/GI tract
ABSORPTION Well absorbed IM / SC / PR / oral - all mucosal surfaces.

High first pass metabolism (individual variability)
DISTRIBUTION Plasma bound but rapidly removed and distributed to highly perfused tissues.
Difficulty crossing blood / brain barrier as amphoteric properties
Main reservoirs - skeletal muscles.
METABOLISM Conjugated by liver with glucuronic acid

Morphine - No. 6 - glucuronide - active metabolite (greater potency than morphine)
EXCRETION Mostly urinary (polar metabolites)

Minor hepatic excretion of metabolites
INDICATIONS 1) Analgesia 2) Anaesthesia - premedication, regional, primary (high does)

3) CHF 4) Cough
CONTRAINDICATIONS Use of pure opioid agonists plus mixed agonist / antagonist - unpredictable effects.
MAO inhibitors - hyperpyrexial coma
SPECIAL PRECAUTIONS Impaired renal, hepatic and pulmonary function.

Head injury and increased intracranial pressure.
Endocrine disease (adrenal insufficiency / hypothyroid.) Elderly
Pregnancy - fetal dependent / new born respiratory depression.
INTERACTIONS MAO inhibitors - high incidence of hyperpyrexial coma

Antipsychotics increased cardiovascular effects. Increased respiratory and CNS depression.
Sedatives and hypnotics increase respiratory and CNS depression.
ADVERSE EFFECTS Dysphonia Constipation Tolerance and dependence

Hypotension Inc. ICP Nausea and vomiting
Withdrawal Urinary retention Respiratory depression
DOSING/ADMINISTRATION IV titratable to analgesic effect

PO MST contin Half the 24 hr IV dose ---.> Rx MST contin twice daily
TOXICOLOGY Respiratory support and symptomatic cares

+ / - naloxone if either diagnostic or if acute overdose (otherwise precipitate acute
withdrawal if abuse)
WITHDRAWAL Onset 6 - 10 hrs symptoms: anxiety/muscle aches/nausea and vomiting lacrimation

SYNDROME Peak 36 - 48 hrs hostility/hyperthermia/diarrhoea/rhinorrhoea
Lasts 5 days yawning/mydrosis/hyperventillation
58
Na Bicarbonate
HISTORY
STRUCTURE/CLASS Alkalinising Agent
PHARMACODYNAMICS Mechanism addn of bicarb react with H+ --> salt

H2C03 <---> H20 + CO2 <---> H+ + HCO3
dissociates to Bicarb ion which neutralizes H+ ion therefore increasing pH
ABSORPTION 1. IV
2. Oral
3. PR
DISTRIBUTION Extracellular buffer of body

T½ 1-2 hrs
METABOLISM
EXCRETION Urine excretion leading to alkaline urine
INDICATIONS 1. Alkalinization in acidosis use with caution eg Diabetes, cardiac arrest

2. Alkalinization of urine in drug overdose e.g. salicylates
3. Severe GI loss
4. Dyspepsia
5. Double contrast study where gas needed
6. “Antidote” to TCA OD
CONTRAINDICATIONS 1. Hypokalemia
2. Hypocalcemia
3. Metab / respiratory alkalosis
SPECIAL PRECAUTIONS 1. CHF - increasing Na+ load leads to incr. LVF

2. Hypocalcemia
3. Renal failure
INTERACTIONS Decreases effects of lithium and salicylates secondary to alkalinization
ADVERSE EFFECTS 1. ? does it worsen intracellular acidosis

2. Extravasation
3. Gastric distension. Fluctuance
DOSING/ADMINISTRATION IV - depends on multiple factors - Age / acidosis severity / weight

usually 2 - 5 mEq/kg 4 - 8 hrs
Oral - 325 - 650 mg 1gm neutralized 12 mEq acid
1 mEq / kg = 1ml /kg of 8.4% solution
TOXICOLOGY OD leads to hypocalcemia, hypokalemia, hypernatremia ---> seizure
59
Naloxone
HISTORY Opium gum contains about 20 alkaloids,one of which is thebain. Thebain is the precursor of
several semi-synthetic opiates including naloxone.
STRUCTURE/CLASS Semi synthetic morphine derivitive with bulky substituant at N-position.
PHARMACODYNAMICS High affinity for mu receptors when given to morphine treated subject completely reverses
the opioid effects in 1-3 mins.
No tolerance to antagonist action.
ABSORPTION Poor efficacy when given orally.

Short duration of action IV - prolonged by IM injection.
DISTRIBUTION Rapidly leaves blood to localize in highly profused tissue.

Half life = 60-90 mins.
METABOLISM Glucuronide conjugation excretion.
EXCRETION Polar metabolites excreted mainly in urine and some in bile.
INDICATIONS Complete / partial reversal of narcotic depression induced by natural / synthetic opioids.
Diagnostic/Therapeutic in carefully selected ODs
Concomittant OD of TCAs or other proconvulsant drugs
SPECIAL PRECAUTIONS May provoke acute abstinence syndrome.

Watch for further symptoms (short action).
INTERACTIONS
ADVERSE EFFECTS Several instances of hypotension, VT and VF , pulmonary oedema in post-op patients with
cardiovascular disease ( ?significance).
Induces an acute withdrawal state in habituated patients
DOSING / ADMINISTRATION 0.1-0.4 mg IV repeated as necessary.
Up to 4mg may be required for non iatrogenic OD
TOXICOLOGY Nil
WITHDRAWAL Nil
SYNDROMES
60
Nitrous-Oxide
HISTORY “Laughing gas” - discovered about 1860
STRUCTURE/CLASS Inhalational anaesthetic / analgesic
PHARMACODYNAMICS 1. Powerful analgesic

2. CVS - direct depression of myocardial contractility. Increased peripheral resistance
3. Low potency (therefore usually used in combination)
MAC > 100%
ABSORPTION Rapid uptake (due to poor tissue solubility)

Low blood/gas coefficient (0.47) therefore quite insoluble in blood
DISTRIBUTION Penetrates rapidly into the brain.

Low solubility therefore reaches high arterial tensions rapidly therefore rapid equilibrium
with brain therefore fast induction
METABOLISM Probably not metabolised by humans
EXCRETION Rapid elimination (“washout”) by lungs
INDICATIONS 1. Analgesia (eg dental / burns / fractrues / dislocations) - potent

2. Adjuvant to inhaled anaesthetics
3. Labour
CONTRAINDICATIONS Trapped gas e.g. pneumothorax, bowel obstruction.
SPECIAL PRECAUTIONS Diffusion hypoxia - large quantities diffused from blood back into alveoli at end of an
anaesthetic, therefore apply O2 mask for 20 minutes after a GA
INTERACTIONS
ADVERSE EFFECTS
DOSING / ADMINISTRATION Mask inhalation - from blue cylinder

Pleasant non irritating gas
TOXICOLOGY Treatment with O2 mask for 20-30 minutes to wash N2O out
Prolonged exposure to N2O causes megaloblastic anaemia (decreased methionine synthetase
activity)
WITHDRAWAL
SYNDROMES
61
Oxygen
HISTORY Discovered by Priestley in 1772
Lavoisier elucidated its role in respiration.
Oxygen therapy introduced by Beddoes in 1794
STRUCTURE/CLASS Colourless, odourless, tasteless gas.

99% V/V of O2 residue = argon with trace of hydrogen or nitrogen
PHARMACODYNAMICS Moves down a stepwise series of pressure gradients from inspired air to the body’s cells and
their mitochondria
Air normally contains 20.9% O2 equivalent at normal barometric pressure to a partial
pressure of 149mm Hg (21kPa)
ABSORPTION Diffuses from alveoli into pulminary capillaries, thence to every body cell
DISTRIBUTION Total body
METABOLISM O2 is essential to respiration of all animal cells.

Permits the process of oxidative phosphorylation in mitochondria converting food fuels into
energy for cell processes
EXCRETION
INDICATIONS Optimise O2 delivery if patients have deficits in O2 transport chain or increased O2

consumption / increased haemoglobin saturation in dyspnoea or respiratory failure/
decompression sickness in divers
CONTRAINDICATIONS High concentration - depress hypoxic drive

Danger of flame or spark especially if O2 under pressure
SPECIAL PRECAUTIONS Titrate O2 dose in chronic CO2 retention relying on hypoxia for respiratory drive
INTERACTIONS
ADVERSE EFFECTS Pulmonary toxicity - decrease in vital capacity, increase cough

CNS toxicity - nausea, mood changes, vertigo, convulsions, loss of consciousness
Retrolental fibroplasia
DOSING / ADMINISTRATION Administered by inhalation by nasal catheter, face mask, endotracheal tube or oxygen tent
Usually to give inspired concentration of 30% but can be up to 100%. Via mask 6L / min
TOXICOLOGY Toxic in high doses. Function of partial pressure and duration of exposure
Symptoms and signs are more rapid with greater PiO2
Toxicity primarily affects the respiratory tract, CNS and eye
Three mechanism postulated 1) formation of free radicals 2) inhibition of enzymes 3) direct
toxic effects on cerebral metabolism
WITHDRAWAL
SYNDROMES
62
Pancuronium
HISTORY This class used on poison arrows of Amazon Basin (causes skeletal muscle paralysis)
STRUCTURE/CLASS Pancuronium bromide - all resemble acetylcholine.

Non depolarising blocking agent of medium duration
= steroid N M blocker
PHARMACODYNAMICS Blocks transmission of motor nerve impulses to striated muscle receptors. Muscle relaxation
for intubation within 2-3 minutes and effects subside after 35-40 minutes
Mechanism - produces surmountable block. At low doses, acts mainly at nicotinic receptor
sites to compete with ACh. At higher doses, also enters the pore of the ion channel to cause
blockade. This further weakens N M transmission and deminishes the ability of the ACh
esterase inhibitors to antagonise these drugs
ABSORPTION IV (highly polar and orally inactive)
DISTRIBUTION Rapid initial distribution phase

Limited Vd (highly ionised)
METABOLISM Not metabolised
EXCRETION Slower elimination phase

Liver and kidney - 50-60%
? biliary
INDICATIONS To induce smooth muscle relaxation for:

- operative manipulations
- intubation
- artificial respiration in ICU patients
CONTRAINDICATIONS Known hypersensitivity

Avoid in pregnancy unless essential
SPECIAL PRECAUTIONS Only use in hospital with resusitation facilities and experienced doctor
Need to be intubated
Correct electrolyte and dehydration problems before use
Increased dose needed with hypothermia (decreased dose with hyperthermia)
Care with myesthenia gravis / polio / hypertension / renal , hepatic, pulminary disease /
tachycardia
Antagonised by Acetylcholine, anticholinesterases and K+ ions
Inhalational anaesthetics - --- augmentation
INTERACTIONS
ADVERSE EFFECTS Rare - usually with overdose. Prolonged apnoea or respiratory depression
Mild / moderate - increased BP / H R
Decreased I O P and induces miosis
Local burning with injection / salivation / transient rashes and wheezing
DOSING / ADMINISTRATION Adults and kids > 1 month - initial 0.04 - 0.1 mg /kg IV, Maintenance 0.01 - 0.02 mg /kg IV at
25-60 minute intervals
Kids ,< 1 month individualize - test dose 0.02 mg / kg
DONT MIX WITH OTHER SOLUTIONS IN SAME SYRINGE
TOXICOLOGY OD - - - prolonged apnoea / respiratory depression / persistent muscle weakness

Treatment - assist ventilation / neostigmine (add atropine) in incremental doses
WITHDRAWAL
SYNDROMES
63
Paracetamol
HISTORY First used in 1893. popular since 1949 . USA no prescription since 1955
STRUCTURE/CLASS N-acetyl-P-aminophenol = coal - tar analgesic (para-aminophenol derivitive).
PHARMACODYNAMICS Still uncertain. Presumably acts by peripheral and central prostaglandin inhibition
ABSORPTION Rapid complete absorption proportional to the rate of gastric emptying.

Peak plasma level 30-60 mins.
DISTRIBUTION Variably protein bound.

Half life 2-3 hrs - therapeutic levels .
Half life > 6 hrs toxic levels.
METABOLISM Hepatic.
> 95% conjugation with glucuronide/ sulphate (children less glucuronidation capacity)
Minor metabolite = N-acetyl-P-benzoquinone.
EXCRETION Renal.
INDICATIONS 1. Analgesia - ? no anti-inflammatory in vivo.

2. Antipyresis - no platelet activity.
CONTRAINDICATIONS
SPECIAL PRECAUTIONS Nil. Large (sub toxic) doses may cause dizziness / excitement / disorientation.
INTERACTIONS Nil.
ADVERSE EFFECTS
DOSING / ADMINISTRATION 20mg / kg qid in children

1g qid in adults
TOXICOLOGY OD 1. Hepato-toxicity
2. Renal toxicity ATN --ARF
Toxic dose 200-250mg /kg (about 15g). Potentially fatal > 25g.
Initially nausea, vomitting, anorexia, abdo pain.
At 2 days increased transaminases, LDH Alk phos, albumin - N
Br, INR may be increased. Eventually coagulopathy causes encephalopathy and death
.
Causes centrilobular necrosis.
Nomogram if 4 hrs post ingestion < 120mcg/ml - unlikely serious.
Toxicity - N-acetyl-P-benzoquinone - electrophilic produces O2 radicals causing lipid
peroxidation leading to hepato-toxicity.
Usually inactivated by reduced glutathione (GSH).
In toxic doses overwhelmsGSH
Treatment - N-acetylcysteine - acts as sulphydryl donor - given as IV loading dose, then IVI x
17 hrs.
WITHDRAWAL
SYNDROMES
64
Penicillin
HISTORY 1929 Fleming noted colonies of staph lysed on a plate
STRUCTURE/CLASS Thiazolidane ring attached to a beta lactam ring as a basic structure
PHARMACODYNAMICS 1. Attachment to specific penicillin binding proteins ( PBPs) that serve as drug receptors on
bacteria
2. Inhibition of cell wall synthesis by blocking transpeptidation of peptidoglycan
3. Activation of autolytic enzymes in cell wall
ABSORPTION Parenteral - complete and rapid (crystalline ‘G’ given IV, benzathine / procaine IM)
Oral differs greatly with different penicillins (phenoxymethyl ‘V’ given O)
DISTRIBUTION Wide distribution in body fluids and tissues except low in CNS, eye, prostate
METABOLISM Half life of penicillin G is 30-60mins in renal failure it may be up to 10 hours
EXCRETION Renal - 10% by glomerular filtration and 90% by tubular secretion to a max of 2g / h in adult.
Also excreted into sputum and milk to levels 3-15 % of those present in the serum.
INDICATIONS Pneumococi , streptococci, treponema , spirochetes , clostridial infections
CONTRAINDICATIONS Hypersensitivity to penicillins / cephalosporins
SPECIAL PRECAUTIONS Patients with allergies, asthma

Severe infections need parenteral treatment as oral absorptiion is unreliable
INTERACTIONS Rare
ADVERSE EFFECTS Anaphylaxis / granulocytopenia / thrombocytopenia / haemolytic anaemia / coagulation

disorders
DOSING / ADMINISTRATION PO 250 - 500mg 4-6 hourly

I M / I V 1 - 2 mega units divided into 2-4 doses. Higher doses need to be given in serious
infections
TOXICOLOGY Anaphylaxis / lethargy / confusion / epileptiform seizures (large quantities)
WITHDRAWAL
SYNDROMES
65
Pethidine
HISTORY
STRUCTURE/CLASS Synthetic phenyl piperedine derivitive.

Opiate agonist
PHARMACODYNAMICS Acting on the opioid receptors of the brain and spinal cord.
Mu, kappa and delta receptors linked to cAMP system and changes Ca++ / K+ flux.
ABSORPTION Oral -absorption good but bioavailability is low.

IM / SC variable absorption.
DISTRIBUTION 60-80%. Bound to plasma proteins.

Crosses placenta.
Excreted in breast milk.
METABOLISM Extensive hepatic metabolism therefore decreased bioavailability(50%).
EXCRETION 5% excreted unchanged in urine.

30% metabolised - norpethidine which is active.
Metabolism in liver - hydrolysis and conjugation.
INDICATIONS Strong analgesic.

Pre-operative / supplement to anaesthesia/ during labour.
CONTRAINDICATIONS Hypersensitivity (to sodium metabisulfite)

Concurrent administration of MAO
SPECIAL PRECAUTIONS Respiritory and circulatory depression

Patients with low blood volume / respiratory compromise.
Hepatic and renal impairment - dose adjustment.
INTERACTIONS Other CNS depressents

MAOIs
INAH- increases side effects of INAH
ADVERSE EFFECTS Nausea / vomitting / respiratory depression / circulatory collapse/ coma/ local tissue
irritation .
Anti-muscarinic effects.
DOSING / ADMINISTRATION Tablets - 50 and 100 mg tablets Parenteral solution
Adults IM/SC 50-150mg 3-4hrs , Slow infusion = 15-35 mg/hr
Children - 1.1 - 1.8mg/ kg . PO / IM / SC 3-4hourly.
TOXICOLOGY Respiratory depression/ nausea/ vomitting/ constipation / tolerance and dependance/
circulatory collapse / seizures.
WITHDRAWAL Signs and symptoms common to opiates.

SYNDROMES Rhinorrhea / lacrimation/ yawning / hypothermia / vomitting/ diarrhoea/ abdominal
cramps.
Symptoms largely subside in 24 hrs.
66
Phenobarbital
HISTORY One of the oldest of currently available anti-epileptics. First used in 1903.
Infrequently used nowadays.
Previously called phenobarbitone
STRUCTURE/CLASS Barbiturate hypnosedative / anti-convulsant.

Chemically similar to phenytoin
pKa is 7.4 → Small change in pH can have large impact on proportion of ionised drug
PHARMACODYNAMICS 1. Enhances GABA receptor mediated current (prolongs opening Cl channels)

2. Blocks excitatory glutamate responses (AMPA receptor).
3. Also blocks high frequency repetitive friring Na+ channels on neurons ( high
concentrations only) + some Ca++ channel blockade
ABSORPTION Well absorbed orally. 100% bioavailability.
DISTRIBUTION 50% protein bound.

Vd = 40L/70kg
Plasma half life = 4 hrs.
METABOLISM Hepatic metabolism slow ( oxidation by hepatic enzymes).
EXCRETION Unchanged in urine 20-30% (Increased with alkalinisation as it is a weak acid)

Rest = liver metabolites (inactive)
Elimination half life = 4-5 days → Risk of accumulation
INDICATIONS Hypnosedative
Anti-convulsant
CONTRAINDICATIONS Porphyria
Cirrhosis
SPECIAL PRECAUTIONS Hepatic or renal failure

Elderly
Respiratory insufficiency
Pregnancy and breast feeding
Withdrawal
INTERACTIONS Additive with CNS depressents + EtOH

Induces hepatic enzymes therefore decreases the effect of warfarin /
anticonvulsants/ digoxin / quinine /chloramphenicol.
ADVERSE EFFECTS Drowsiness / tolerance/ dependency / rash/ ataxia / bone marrow depression (rare)
DOSING / ADMINISTRATION Hypnotic - 60-100mg nocte

Sedative - 15-30mg q 2-4hourly
Anticonvulsant - 60-400mg/day (loading dose 15mg/kg over 30 minutes)
TOXICOLOGY Supportive treatment / repeated charcoal/ urinary alkalinisation

Flumazenil - antidote (not greatly used) may be partially effective
Symptoms - Disinhibition , lethargy, stupor, coma, hypotension, small pupils,
hypothermia, nystagmus,
WITHDRAWAL SYNDROMES Initially: ↑ Anxiety, tremor, twitch, nausea and vomiting

Later: Convulsions, severe delirium, hallucination, psychosis
Treatment: Propranolol
67
Phenytoin
HISTORY Oldest non-sedative anti-epileptic. Introduced 1938. Known previously as
diphenylhydantoin.
STRUCTURE/CLASS Diphenyl-substitued hydantoin.

Anti-epileptic drug.
Class 1B anti-arrythmic
PHARMACODYNAMICS Reduces Na+, K+ and Ca++ conductances , membrane potentials, concentration of amino
acids and neurotransmitters noradrenaline, acetylcholine and GABA.
Blocks sustained high frequency firing in neurons .
Binds to and prolongs inactivated Na+ channels.
ABSORPTION Highly dependant upon dosage form. Nearly complete.

Time to peak 3-12 hrs.
DISTRIBUTION Highly plasma protein bound.

Concentration in CSF proportional to plasma levels.
Accumulates in endoplasmic reticulum of brain, liver, muscle and fat
Vd = 45L/70kg
METABOLISM Parahydroxylation plus subsquent conjugation with glucuronic acid.

Metabolites inactive
EXCRETION Elimination is dose dependant. Cl = Vmax / (Km+ Cp)

Excreted in urine
Half life = 12-36 hrs.
INDICATIONS Partial and generalized tonic / clonic seizures.

Digitalis induced arrhythmias.
CONTRAINDICATIONS Hypersensitivity
In pregnancy: Fetal hydantoin syndrome
SPECIAL PRECAUTIONS Caution in liver impairment
INTERACTIONS Displaced from plasma proteins by other highly bound drugs e.g. sulphonamides.
Induces microsomal enzymes.’
Phenobarbitone and cabamazepine cause decrease in steady state.
Isoniazid inhibits metabolism
ADVERSE EFFECTS Nystagmus/ diplopia/ ataxia/ sedation/ gingival hyperplasia/ hirsuitism/ osteomalacia/
idiosyncratic rash/ fever / agranulocytosis.
DOSING / ADMINISTRATION Children: 5mg/kg/day

Adults: 300mg/day (increase by 25mg each time)
Status epilepticus: 13-18mg/kg (~1000mg for 70kg person)
 Inject not faster than 50mg/min
 In saline (precipitates in glucose)
TOXICOLOGY Lethal dose 2-5g.

Comatose, fixed pupils, hypotension.
Death secondary to respiratory depression.
WITHDRAWAL SYNDROMES Usually gradual discontinuation.

Watch for recurrence of seizures
68
Prazosin
HISTORY Originally invented to be direct acting vaso dilator
STRUCTURE/CLASS Selective alpha I antagonist (little alpha 2 effect) About 1,000 times difference in affinity.
Contains a piperazinyl quinazoline nucleus.
PHARMACODYNAMICS Relaxation of both arterial and venous smooth muscle.

Decreases BP. They tend to improve lipid profile and also glucose - insulin metabolism and
may thus reduce the risk of
atheroschlerosis. There is no reflex increase HR and CO - it reduces preload and is Alpha I
selective. There may also be a central component to this effect.
ABSORPTION 68% oral bioavailibility. Has a first pass depletion.
DISTRIBUTION 98% protein bound in plasma. Vd = 42 l / 70 kg. Conditions altering plasma protein profile
(e.g. acute inflamatory
conditions) will alter prazosin effects.
METABOLISM 1% excreted unchanged in urine. Half life = 3 hrs. Extensively metabolised in liver. First pass
effect is large.
EXCRETION Renal excretion.
INDICATIONS Primary systemic hypertension.

Congestive cardiac failure - reduced preload and afterload.
Adjunct in bladder outlet obstruction e.g. prostatic hyperplasia.
CONTRAINDICATIONS Renal failure.

Hepatic compromise.
SPECIAL PRECAUTIONS Hypertension

Aged patients (decreased clearance)
INTERACTIONS Any drug causing hypovolaemia - e.g. diuretics.
ADVERSE EFFECTS First dose hypotension and syncope

Postural hypotension. Headache, diziness, drowsiness and nausea.
DOSING / ADMINISTRATION Up to 20 mg / day

1 - 5 mg PO TDS
TOXICOLOGY
WITHDRAWAL Many patients become tolerant to the drug during long term medication.
SYNDROMES
69
Prilocaine
HISTORY
STRUCTURE/CLASS Amide LA. Potency approx. = to lignacaine.

pka 7.7
PHARMACODYNAMICS Binds to intracellular end of Na+ channel - reversible blockade of impulse generation. Blocks
pain and other sensation “membrane stabilizer”
ABSORPTION Absorbed more slowly than lignacaine secondary to lesser vasodilator effect.
Hcl salt for stability+ solubility.
DISTRIBUTION 55% protein binding. Fat:water partition co-efficient 0.9.

Widely distributed after IV bolus ? sequestered in fat. Initial rapid distribution phase due to
uptake by highly profused organs e.g. brain, liver, kidney, heart. Slower distribution phase to
moderately profuse tissue e.g. muscle, gut.
METABOLISM Much less prone to hydrolysis in plasma than esters hence longer half life.
Amide linkage hydrolized by amidases mainly in liver (also kidneys, lungs, faster than
lignacaine).
Toxicity possible in patients with liver disease - longer duration of action and increased peak
levels.
EXCRETION LA + metabolites excreted in urine.
INDICATIONS Local anaesthetic - intercostal / brachial/ femoral/ axillary/ epidural/ spinal blocks/ IVRA/
local infiltration.
CONTRAINDICATIONS Hypersensitivity to amide LA/ infection / septicemia/ coagulation or bleeding disorders/

anticoagulants/ uncontrolled hypotension.
SPECIAL PRECAUTIONS Full resuscitation equipment must be available.

Inject slowly and lowest possible dose. Anticipate hypotension decreased heart rate with
spinal injection. Can accumulate in repeated injection.
Decreased dose in elderly, debilitated, accutely ill.
INTERACTIONS 1. Halothane, cimetidene, betablockers decrease hepatic bloodflow therefore decrease

metabolism. Halothane also inhibits microsomal enzymes.
2. May potentiate cardiac effects of antiarrythmics including lignocaine, phenytoin.
ADVERSE EFFECTS Prolonged blockade / parasthesiae / weakness / paralysis/ allergy/ restlessness/

disorientation,/ numbness/ nausea &vomitting/ nervousness/ tremor/ tinitus/ fits/coma/
respiratory depression.
High doses can cause methaemoglobinaemia
DOSING / ADMINISTRATION Use lowest possible dose + adrenaline if not contraindicated.

Dose: 400mg / 70kg plain , 600mg/70kg with adrenaline.
Topical (EMLA) - 1hr max 2hrs.
IVRA 5mg/kg plain max. LA / regional max 8.5mg/kg . Adrenaline 1:200000.
TOXICOLOGY Usually secondary to high levels or inadvertent subarrachnoid injection.`’
CNS - excitation/ nervousness/ diziness/ blurredvision/ tremors/ drowsiness/ convulsions/
coma/ resp arrest.
CVS - can lead to peripheral vaso dilatation, hypotension, myocardial depression, cardiac
arrest. DO NOT TREAT WITH PHENYTOIN
WITHDRAWAL Nil Known.
SYNDROMES
70
Procainamide
HISTORY
STRUCTURE/CLASS An analogue of procaine, local anaesthetic. Class IA. Antiarrythmic.

Lacks quinidine's vagolytic and alpha adrenergic blocking activity
PHARMACODYNAMICS Is a sodium channel blocker and also prolongs cardiac action potential.
Decreases automaticity, increase refractory period, slows conduction.
May prolong AP by blocking K+ outflow.
Effective concentrations = 3 - 14 mg / litre toxic at greater than 14 mg / litre.
ABSORPTION PO, IV, IM. 75% bioavailability given PO.
DISTRIBUTION 16% bound in plasma. Vd = 130 litre / 70 kg.
METABOLISM Major metabolite N acetyl procainamide - weak Na + channel blocker but also increases action
potential.
Hepatic metabolism. Combination with N acetyl cystine.
EXCRETION Half life is 3 - 4 hrs. Excreted both unchanged and as a metabolite. Reduced in renal failure.
67% excreted
unchanged. Clearance = 36 litre / hr / 70 kg.
INDICATIONS Acute therapy of supraventricular and ventricular arrythymias. May be the second choice,
after lignocaine, for ventricular arrythmias post MI.
CONTRAINDICATIONS Sick sinus syndrome - depresses the pacemaker activity of the SA node.
SPECIAL PRECAUTIONS Renal disease - can get increased plasma concentrations leading to toxicity.
INTERACTIONS Cimetidine and amiodarone reduce renal excretion by competing at the transport site in the
kidney.
ADVERSE EFFECTS Hypotension, marked slowing of conduction. Dose related nausea. Torsades de pointes.
0.2% bone marrow aplasia (not dose related). Development of new arrythymias. Drug
induced SLE. Renal involvement unusual.
DOSING / ADMINISTRATION Drug is inconvenient to take as its rapid elimination requires administration three to eight
times daily. Total dose 2 - 5g / day.
TOXICOLOGY In patients who are slow acetylators the procainamide induced SLE develops more rapidly
than in fast acetylators
due to decreased metabolism rate.
WITHDRAWAL
SYNDROMES
71
Prochlorperazine
HISTORY Synthesized in the late 19th century.
Clinically used since 1950s.
STRUCTURE/CLASS Phenothiazine (piperazine) - antipsychotic / neuroleptic.
PHARMACODYNAMICS Dopamine receptor blockade.

Five types dopamine receptors. D2 blockade most corrolates with EP side effects.
Especially in dopaminergic receptors in CTZ of medulla.
Also anticholinergic, alpha blocker and sodium channel blocking effects
ABSORPTION Incomplete absorption with considerable first pass effect.

? 30% bioavailability.
DISTRIBUTION Highly protein bound - 92-99%. Highly lipid soluble.

Vd > 7L/kg.
Half life (alpha) = 2 hrs .
Half life (beta) = 10-20hrs.
METABOLISM Hepatic - multiple metabolites e.g. glucuromide - mostly inactive.
EXCRETION Renal - of polar metabolites.
INDICATIONS 1. Anti-emetic.
2. Not indicated for psychotic episodes - otheranti-psychotics better tolerated.
3. Migraine
CONTRAINDICATIONS
SPECIAL PRECAUTIONS Possibly seizure disorders (more important with chlorpromazine)
INTERACTIONS 1. Pharmacodynamic rather than pharmacokinetic especially with additive medicines -

sedatives/ alpha blockade.
2. Enzyme inducing medicines e.g. phenabarbitone/ phenytoin may increase metabolism.
ADVERSE EFFECTS 1. Autonomic NS = muscarinic blockade - dry mouth/ urinary retention/constipation/ loss of
accommodation.
2. Autonomic NS = alpha blockade - orthostatic hypotension/ impotence.
3. CNS effects = dopamine receptor blockade .
4. CNS effects = increased sensitivity dopamine receptors.
5. CNS effects = toxic confusional state.
6. Endocrine effects = hyperprolactinimia.
7. Rare - cholestatic jaundice/skin reactions/ blood dyscrasias
8. Neuroleptic malignant syndrome.
DOSING / ADMINISTRATION PO(5mg tds) /PR / IM /IV(12.5mg slowly)
TOXICOLOGY Overdose - drowsiness/agitation/coma/decreased deep tendon reflexes/ myosis/

hypotension/ hypothermia.
?? gastric lavage (Secondary to decreased gastric emptying) vs charcoal.
Supportive treatment.
WITHDRAWAL
SYNDROMES
72
Promethazine
HISTORY Available since about 1950. A 1st-generation H1 receptor antagonist.
Increasingly being replaced new, less lipid soluble (and hence less CNS active) H1 blockers.
STRUCTURE/CLASS Phenothiazine derivative. Most antihistamines share a common core structure with a number
of side group substitutions.
PHARMACODYNAMICS H1 receptor antagonist (negligible H2 effect) causes antihistamine/ sedation as well as anti
nausea and antiemetic
Anticholinergic, alpha blocker, antiseratoninergic, Na + channel blocker and hence local
anaesthetic, antidopaminergic
ABSORPTION Well absorbed (~90%), but with low oral bioavailability (25%) due to a significant first pass
effect
DISTRIBUTION Widely distributed to all tissues and CNS

Vd > 5L/ kg
METABOLISM Liver metabolism is extensive
EXCRETION Largely urine excretion

Serum half life 4 - 6 hours but clinical effects are prolonged (up to 24 hours)
INDICATIONS Allergy - Urticaria, hayfever, adjunct in anaphylaxis

Antiemetic, anti migraine, motion sickness, sedative, local anaesthetic
Anxiolytic
CONTRAINDICATIONS
SPECIAL PRECAUTIONS Will potentiate other neurosedative agents

Use very cautiously if given IV due to risk of transient hypotension
INTERACTIONS Potentiates other sedatives
ADVERSE EFFECTS Sedation, anticholinergic (dry eyes, dry mouth, blurred vision, retention) , photosensitizer,
postural hypotension, extrapyramidal.
Rare - cholestatic jaundice / agranulocytosis
DOSING / ADMINISTRATION Orally 0.25 mg -0.75 mg / kg /day (often dose at night to minimize sedation)
IM 0.25 - 0.5 mg/ kg. Not for SC use in undiluted form
IV 0.25 mg / kg IV slowly
TOXICOLOGY Usually depressed conscious state, pronounced anticholinergic effects

Can have paradoxical excitation with seizures or central anticholinergic syndrome
Tachyarrythmias and hypotension may occur
WITHDRAWAL Not reported

SYNDROMES
73
Propranolol
HISTORY Black & Stephenson 1962.
STRUCTURE/CLASS Beta blocker. Structure similar to agonists.Lipophilic . Two aromatic rings.
PHARMACODYNAMICS Non selective beta adrenergic antagonist, no agonist activity. A central 5 HT blocker,
negative chronotropic and inotropic activity. Decreased cardiac output and increased
peripheral resistance. With long term use TPR returns to normal. Reduces sinus rate,
decreases automaticity of ectopic pacemakers, slow atrial and AV nodal conduction. Not felt
to be a membrane stabiliser at normal doses. Lowers BP ? how. May reduce plasma renin
release. May be central.
ABSORPTION Almost completely absorbed PO but only 25% bioavailibility due to first pass.
DISTRIBUTION Large Vd about 4 l / kg. Readily enters CNS. 90% found in plasma
METABOLISM Extensively metabolised. Half life is 4 hrs.
EXCRETION Metabolites excreted by kidney. Less than 1% unchanged.
INDICATIONS Hypertension and angina. 40 - 80 mgs / day initially and increase up to 320 mg / day.
Class II antiarrythmic. May use with glaucoma.
Used post MI Hyperthyroidism, migraine prophylaxis. Anxiety.
CONTRAINDICATIONS Asthma
Cardiac failure (but low doses now being trialed)
SPECIAL PRECAUTIONS IDDM. May mask symptoms of hyperthyroidism.

Peripheral vascular disease.
Age - there is an age related hepatic clearance reduction.
INTERACTIONS Beta agonists. Disopyramide

Antiacids - reduce plasma concentration
Other - enhance negative inotropic effects of some antiarrythmics - verapamil
ADVERSE EFFECTS Profound bradycardia. Hypotension.

Hypoglycaemia. Exacerbation of asthma. Increased LDL / HDL ratio.
Nausea, vomiting, diarrhoea. Nightmares and insomnia.
DOSING / ADMINISTRATION Twice daily, despite low half life. (complex pharmacokinetics). May use slow release once
daily dose.
TOXICOLOGY Atropine may reverse profound bradycardia if given in overdose.
Glucagon is considered the specific antidote.
WITHDRAWAL Some patients, after prolonged treatment: Nervousness, tachycardia, exacerbation of angina,
SYNDROMES hypertension. May cause MI I thus not to be abruptly discontinued. May be due to "up
regulation" of beta receptors.
74
Propofol
HISTORY Has largely replaced sodium thiopental for induction of anaesthesia as recover is
more rapid
STRUCTURE/CLASS Diisopropylphenol short acting IV anaesthetic

A characteristic milk-like appearance of its IV preparation
PHARMACODYNAMICS Mechanism of action poorly understood - Likely potentiation of GABAA
ABSORPTION IV
DISTRIBUTION Rapid. Onset of action 30 seconds

Half-life 2-8 minutes
Slow redistribution from poorly perfused tissues
METABOLISM Liver metabolism - --- Glucuronic / sulphuric conjugates

(+ other tissues)
EXCRETION 1 - 3 hours
renally excreted < 1% unchanged
Clearance = 1.5 - 2L / min
INDICATIONS Anaesthesia
Sedation in ventilated patients
Advantages - rapid onset and recovery / effective for long sedation / vomiting post
op uncommon.
SPECIAL PRECAUTIONS Convulsions with epileptics organ failure (cardiac / hepatic / renal / resp)
Bradycardia (vagolytic) hypovolaemia
Pregnancy and delivery ? lactation
Immediate administration as good culture medium
INTERACTIONS none found
ADVERSE EFFECTS Hypotension (decreased TPR) anaphylaxis

Transient apnoea sexual disinhibition
Convulsions nausea /v omitting / headache (rare)
DOSING / ADMINISTRATION Induction - titrate 14mg every 10seconds. About 2 - 2.5 mg/ kg
Maintenance - continuous infusion 4 - 12 mg / kg/ hour. Repeat bolus 25-50 mg PRN
TOXICOLOGY Cardiorespiratory depression.

Treatment - ventilate / plasma expanders / inotropes
75
Red Back Spider Antivenom
HISTORY Red Back or Black Widow Spider (Latrodectus mactoms)
Only female potentially dangerous to man. Neither sex aggressive unless guarding egg sacs
STRUCTURE/CLASS Equine derived antibodies to red back spider antivenom.
PHARMACODYNAMICS Specific venom neutralizing immunoglobulins
ABSORPTION IM (usually effecitve in most cases)

IV if severely envenomated (slow infusion) / rarely used
DISTRIBUTION
METABOLISM
EXCRETION
INDICATIONS Bitten by red back spider - will have definite / distressing evidence of envenomation.
If 24 hours have elapsed with only mild local effects - can withhold treatment
NB : Beware of child with acute illness and sudden onset of painful skin lesion
The venoms major affects are neurotoxic. Can be given up to 10/7 post bite.
SPECIAL PRECAUTIONS Anaphylaxis (only give in places equipped for treating anaphylaxis)
INTERACTIONS
ADVERSE EFFECTS Anaphylaxis particular if previously treated with horse derived serum.
Late serum sickness.
DOSING / ADMINISTRATION 1. IV antihistamine

2. SC adrenaline 0.25 - 0.5 mg if previous anaphylaxis
3. 15 minutes after antihistamine (not at adrenaline site) 500 units IM
4. If no improvement in one hour repeat dose
5. If severe envenomation give IV 500 units diluted 1:10 Hartmanns over 30 minutes.
WITHDRAWAL
SYNDROMES
76
Salbutamol
HISTORY
STRUCTURE/CLASS Beta 2 selective adrenoceptor agonist used in reversible airway obstruction due to asthma or
CORD
PHARMACODYNAMICS Peak effect : oral 2-3 hours

nebulizer / inhalation 0.5 - 2 hours
Duration : oral = 4-6 hours
nebulizer/ inhalation = 3-4 hours
ABSORPTION Aerosol deposition depends on particle size, pattern of breathing and geometry of airways
80% deposited in mouth or pharynx
Absorption can be increased by held inspiration
DISTRIBUTION Half life : inhalation = 3.8 hours

oral = 2.7 - 5 hours
METABOLISM By liver to an inactive sulphate.

28% appears in urine unchanged
EXCRETION 28% in urine unchanged
INDICATIONS Asthma CORD

Adjunct in hyperkalaemia management.
CONTRAINDICATIONS Hypersensitivity to salbutamol, adrenergic amines or any ingredients
SPECIAL PRECAUTIONS Hyperthyroidism / diabetes

Coronoary insufficiency or hypertension
Excessive use may result in tolerance
INTERACTIONS Decreased effects beta adrenergic blockers

Increased therapeutic effect with ipratropium
Increased toxicity with MAOIs , tricyclics , sympathomimetics
ADVERSE EFFECTS Tachycardia /. palpitations

GI upset/ nausea
Nervousness / CNS stimulation/ / diziness
DOSING / ADMINISTRATION Metered dose inhaler - children 1- 2 puffs qid / adults 2 puffs qid
Nebulizer - children 2.5 mg qid / adults 5 mg qid
Also oral syrup and tablet
IV 250 - 500 mcg stat then approximately 5 mcg per minute.
TOXICOLOGY Hypertension, tachycardia, angina , hypokalaemia and tachyarrythmias
WITHDRAWAL Can use cardioselective beta adrenergic blocker (atenolol or metpprolol) watch for
SYNDROMES bronchospasm.
77
Snake Antivenoms
HISTORY Developed through pioneering work at CSL in the 1950s
STRUCTURE/CLASS Prepared by immunizing horses with specific snake venoms at increasing doses over a long
period of time. Serum is fractionated to produce a pure equine immunoglobulin . Different
antivenoms are produced for different snakes (monovalent) or groups of snakes (polyvalent)
PHARMACODYNAMICS Antivenoms are immunoglobulins that bind and neutralize the snake venoms preventing their
neurotoxic, coagulant, haemolytic and myolytic actions
ABSORPTION Always given by IV infusion.
DISTRIBUTION No firm data
METABOLISM No firm data
EXCRETION Presumably renal
INDICATIONS Snake bite where envenomation has occurred. This may be judged on symptoms and signs
alone or on the basis of venom detection assay or pathology testing (especially clotting
disorders).
CONTRAINDICATIONS Essentially none
SPECIAL PRECAUTIONS Routine premedication with IV steroid , slow IV antihistamine and SC adrenalin
Must not be given IM
Always given by slow and dilute IV infusion.
INTERACTIONS Compatible with all conventional IV fluids

Usually given diluted in N Saline or Hartmanns
ADVERSE EFFECTS Anaphylaxis early. Especially likely in those previously treated with antivenom or other horse
proteins. Complement like activity may produce an anaphylactoid reaction without previous
exposure. Delayed serum sickness occurs.
DOSING / ADMINISTRATION An ampule contains sufficient antivenom to neutralize the average bite of one snake.
Dilute the antivenom in 1000mls N Saline and infuse over 30 minutes. Repeat as required to
revers snake venom effects. Same dose in children and adults.
TOXICOLOGY
WITHDRAWAL
SYNDROMES
78
Sotalol
HISTORY
STRUCTURE/CLASS Non selective beta antagonist, but antiarrythymic effects are independent
Is a K + channel blocking agent. Class III antiarrythymic.
PHARMACODYNAMICS Beta blocker. K + channel blocker. Prolongs action potential.

Decreases automaticity. Slows AV nodal conduction and prolongs AV node refractory period.
ABSORPTION Well absorbed greater than 90% bioavailability.

Peak in 2 - 3 hrs.
DISTRIBUTION Throughout body (is lypophilic), including CNS.

6% plasma protein bound. Crosses the placenta, found in breast milk. Vd = 2 litres / kg
METABOLISM Half life is 8 hrs.
EXCRETION By kidney, greater than 75% unchanged.
INDICATIONS Supraventricular and ventricular arrythymias.
CONTRAINDICATIONS As with beta blockers

Asthma
IDDM
SPECIAL PRECAUTIONS Hypokalaemia (increases side effects).

Also some of the beta blockers.
Renal failure, cardiac failure, peripheral vascular disease, hypotension
INTERACTIONS With decreasing serum K + get increasing torsades de pointes ---> with diuretics.
ADVERSE EFFECTS Beta blockade side effects - hypotension, hyperglycaemia, bradycardia, worsening of asthma
and peripheral vascular disease.
Antiarrythymic ----> torsades de pointes due to prolongation of QT. Retroperitoneal fibrosis
reported.
DOXING / ADMINISTRATION BD dosage, 80 - 320 mgs given orally
IV infuse 40 - 120 mgs over 15 - 30 minutes
TOXICOLOGY In overdose severe bradycardia.
Other cardiac arrythymias
WITHDRAWAL Rebound beta agonist activity (endogenous) on withdrawal.

SYNDROMES
79
Spironolactone
HISTORY
STRUCTURE/CLASS Potassium sparing diuretic.

Aldosterone antagonist
Moderate anti-androgen agent
PHARMACODYNAMICS Competitively binds receptors at aldosterone dependent Na+ /K+ exchange site in distal
convoluted rental tubule
Increases excretion Na+ and H2O while K+ is retained
Slow onset action - full therapeutic effect takes several days
ABSORPTION Bioavailability > 90%

Absorbed well from gut
DISTRIBUTION More than 90% bound to plasma proteins

Half life = one hour after single dosing
METABOLISM Rapidly and extensively metabolized

24-30% metabolized to canrenone
Also sulphur containing metabolites
Activity of canrenone = 10 - 33% that of spironolactone
EXCRETION Hepatic / some renal
INDICATIONS Oedema / diuretic induced hypokalaemia

Hypertension / primary aldosteronism
Malignant hypertension / hirsuitism
CONTRAINDICATIONS Acute renal insufficiency

Anuria / pregnancy
Hyperkalaemia
SPECIAL PRECAUTIONS Other forms of K+ supplementation

Impaired renal function
INTERACTIONS Risk of hyperkalaemia increased with indomethacin or ACE inhibitors

Inhibits clearance of digoxin
ADVERSE EFFECTS GI symptoms / drowsiness / lethargy / rashes

Headache/ mental confusion / ataxia
Amennorrhoea / impotence / gynaecomastia
DOSING / ADMINISTRATION Tablet 25mg / 100mg
TOXICOLOGY True toxic effects not reported

Hyperkalaemia main problem
Can be treated with IV glucose / insulin
WITHDRAWAL
SYNDROMES
80
Streptokinase
HISTORY Produced by streptococci.
Urokinase produced by kidney.
STRUCTURE/CLASS Fibrinolytic drug.
PHARMACODYNAMICS SK combines with plasminogen = activator complex. ‘

Sk/plasminogen catalyzes plasminogen producing plasmin.
1. Fibrin --- fibrin split products.
2. Fibrinogen --- FDP.
Urokinase directly converts plasminogen to plasmin.
APSAC = anisoylated plasminogen: SK activator complex - after administration acyl group
hydrolizes therefore enzyme active site exposed.
ABSORPTION IV infusion
DISTRIBUTION In intravascular space.
METABOLISM Half life =- 23 mins

In part inactivated by antistreptococal antibodies.
EXCRETION No known metabolites - mechanism of elimination unclear.
INDICATIONS 1. Acute myocardial infarction.

2. Pulmonary embolism - especially with significant CVS / resp compromise.
3. Proximal DVT (decreased post phlebytic syndrome).
4. IV access de-clotting
CONTRAINDICATIONS 1. Recent haemorrhage or haemorrhagic diathesis.
2. Recent (within 2/12) CVA; intracranial or intraspinal surgery.
3. Recent surgery up to 10th post-op day
4. High anti-strepAbs (e.g. Rheumatic fever, post-strep GN)
5. Uncontrolled hypertension > 200/110.
6. Other instrumentations or past bleeding conditions.
SPECIAL PRECAUTIONS 1. Can be repeated within 5 days, but not between 5 days to 1 year (?longer).
2. Hypotension - slowing or cessation of infusion.
3. Reperfusion arrythmias in 1-10%
INTERACTIONS Increased bleeding with other anticoagulants.
ADVERSE EFFECTS 1. Bleeding - treatment is stopping infusion / pressure/ FFP. May use aminocaproic acid
which inhibits plasminogen --plasmin.
2. Anaphylaxis - secondary to antistreptococcal antibodies.
3. Hypersensitivity reactions.
DOSING / ADMINISTRATION MI - 1.5millionUnits over 30-60 mins.
PE - 250, 000Units over 30 mins --- 100,000Units/hour for 24 hrs
IV cannulae - 250,000Units in 2mls - leave in situ for 2 hrs.
TOXICOLOGY
WITHDRAWAL
SYNDROMES
81
Sumatriptan
HISTORY Developed in 1984.
STRUCTURE/CLASS 5H T agonist
PHARMACODYNAMICS 5H Tid/ 5 HT ib receptors cause constriction of intracranial a- v anastomoses

Autoreceptors - block the release of proinflammatory neurotransmitters.
ABSORPTION SC - peak level 12 minutes (BA - 97%)

Oral - peak level 2 hours (BA - 14%)
Half life = 2 hours
DISTRIBUTION Protein binding = 14-21%.

Reasonably wide distribution in tissues
METABOLISM An isoenzyme of MAO
EXCRETION Metabolites excreted in the urine.
INDICATIONS Migraines
Cluster headaches
CONTRAINDICATIONS Patients with signs and symptoms of IHD / uncontrolled hypertension / hypersensitivity /
ergot compounds
SPECIAL PRECAUTIONS Drowsiness may occur.

Underlying cardiac disorders
Impaired hepatic / renal function
INTERACTIONS Ergotamine - because of additive effects.
ADVERSE EFFECTS Transient symptoms including chest pain and tightness in the throat
DOSING / ADMINISTRATION SC = 6mg injection. If symptoms recur a further dose can be given within 24 hours.
PO = 100mg tablets. Maximum of 3 in 24 hours.
TOXICOLOGY Moniter and supportive treatment for at least 10 hours.
WITHDRAWAL
SYNDROMES
82
Suxamethonium
HISTORY
STRUCTURE/CLASS Skeletal muscle relaxant

Non competitive, depolarizing
PHARMACODYNAMICS Mechanism : causes depolarization of motor end plate at myoneural junction which causes
sustained flaccid skeletal muscle paralysis produced by state of accommodation that develops
in adjacent excitable muscle membranes.
Phase l block (depolarizing)
Phase ll block (desensitizing)
ABSORPTION IM or IV
DISTRIBUTION
METABOLISM Rapid hydrolysis by plasma cholinesterase therefore only small fraction reaches N M J . Nil or
little plasma cholinesterase at motor end plate.
EXCRETION Action terminated by diffusion away from end plate into extra cellular fluid
INDICATIONS 1. For muscle relaxation for intubation after 30 secs. (IV)

2. For rapid insertion of ETT
3. If short acting muscle relaxant is all that will be needed
CONTRAINDICATIONS Pseudocholinesterase deficiency
SPECIAL PRECAUTIONS Unstable if unrefrigerated greater than 14 days.

Full resuscitation or theatre facilities.
Possible decreased pseudocholinesterase levels ---- pregnancy / OC pill / liver disease/
certain carcinomas / muscular dystrophy / burns.
INTERACTIONS Increased toxicity with anticholinesterases (eg neostigmine) plus sux may cause
cardiorespiratory arrest.
Cyclophosphamides / OC pill / lidocaine / pancuronium and procaine enhance or prolong
effects of suxa.
Increased N M block with inhaled anaesthetics / LA / Ca++ channel blockers / antiarrythmics/
antibiotics / immunosuppressants.
ADVERSE EFFECTS CVS - “second dose” bradycardia, arrythmias. (Decreased doses cause decreased H R and CO.
Increased doses cause increased H R and CO.)
Hyper kalaemia / increased IO P / increased intragastric pressure/ postop muscle pain.
DOSING / ADMINISTRATION IM or IV paeds - 1-2 mg / kg adults - 1 mg / kg

Duration 4-6 minutes (IV) 10-30 minutes (I M)
TOXICOLOGY OD causes resp paralysis / cardiac arrest / bradyarrythmias.

Treatment = supportive - --- don’t treat with anticholinesterases
WITHDRAWAL
SYNDROMES
83
Tetanus Immunoglobulin
HISTORY Prepared from blood obtained from voluntary donors.
STRUCTURE/CLASS Human tetanus immunoglobulin

Sterile solution 160 mg/ ml plasma proteins
PHARMACODYNAMICS
ABSORPTION
DISTRIBUTION Peak serum levels 2- 4 days after I M injection

Half life = 3 weeks.
METABOLISM
EXCRETION
INDICATIONS Passive protection of individuals who have sustained a tetanus - prone wound and with absent
or doubtful history of tetanus immunisation.
CONTRAINDICATIONS People with isolated IGA deficiency.

Known allergic response to Thiomersal.
SPECIAL PRECAUTIONS Not IV. Check not into blood vessel.

Previous history of hypersensitivity reactions to human immunoglobulin preparations.
Give Tetanus Toxoid at a different site.
INTERACTIONS Can interfere with live attenuated virus vaccines.
ADVERSE EFFECTS Reactions uncommon

Local tenderness at site, mild pyrexia , malaise and urticaria.
DOSING / ADMINISTRATION Vials for IM injection contain 250iu tetanus antibody.
TOXICOLOGY No information available.
WITHDRAWAL
SYNDROMES
84
Tetanus toxoid
HISTORY Derived from Clostridium tetani grown in media and detoxified by use of formaldehyde.
STRUCTURE/CLASS Tetanus toxoid aluminium phosphate - adsorbed.

Often combined with diptheria vaccination
PHARMACODYNAMICS
ABSORPTION Give I M. and NOT S.C.
DISTRIBUTION Serum antitoxin levels 0.01 antitoxin units

Protection lasts for ten years
METABOLISM
EXCRETION
INDICATIONS Prevention of tetanus infection
CONTRAINDICATIONS Hypersensitivity to components of vaccine
SPECIAL PRECAUTIONS Shake container and use immediately.

Care with thrombocytopaeina and concomittant warfarin.
INTERACTIONS Immunosuppressive therapy
ADVERSE EFFECTS Local reaction at injection site.
DOSING / ADMINISTRATION Three doses of 0.5ml at intervals of 6-12 weeks between 1st and 2nd doses and 6-12 months
between 2nd and 3rd doses.
TOXICOLOGY Nil known .
WITHDRAWAL
SYNDROMES
85
Thiopentone
HISTORY
STRUCTURE/CLASS Ultra short acting , rapid acting hypnosedative barbiturate

Weak acid.
PHARMACODYNAMICS 1. Molecular pharmacology: Acts at GABA - R complex but not at GABA - R binding site
Cl - channel
At least 3 different subunits alpha, beta, gamma
2. Neuropharmacology : Facilitates action of GABA (multiple sites)
(a) Increase in duration of Cl- channel opening
(b) GABA mimetic at high concentration
(c) Depresses action of excitatory neurotransmitters
ABSORPTION IV only.
DISTRIBUTION Rapidly crosses blood brain barrier - hypnosis in circulation (if sufficient dose)
Rapid redistribution into muscle / fat thence all body tissues
Therefore short acting
METABOLISM Slower than distribution

Liver metabolism 12-16% / hour
EXCRETION Renal - 1% excreted unchanged

Elimination half life = 9 hours
Therefore decreased effect = redistribution effect.
INDICATIONS Anaesthesia
Neurosurgical patients with raised IO P 1.5 mg - 3mg / kg
Convulsive states
CONTRAINDICATIONS Absolute : Absence of suitable veins due to extravasation - necrosis or intraarterial - gangrene
/ hypersensitivity / status asthmaticus / latent or manifest porphyria.
Relative : Hypotension / Addison’s / asthma / myxoedema / myasthenia / anaemia.
SPECIAL PRECAUTIONS Avoid extravasation

Crosses placenta / into breast milk
INTERACTIONS Probenicid : prolongs action of thiopentone

Midazolam : synergism
Aminophylline : antagonism
Opioids : decreased antinociception
ADVERSE EFFECTS Respiratory / cardiac depression Renal failure
Arrythmia (especially if PC O 2 increased) Haemolytic anaemia
Anaphylactoid Bronchospasm Laryngospasm
DOSING / ADMINISTRATION 50-75 mg IV at 20-40 second intervals. 25-50 mg IV maintenance if patient moves.
Rapid induction 3 - 5 mg / kg
TOXICOLOGY Hypotension
Laryngospasm / respiratory difficulties
Supportive O2
WITHDRAWAL
SYNDROMES
86
Thioridazine
HISTORY
STRUCTURE/CLASS Phenothiazine neuroleptic

Piperidine - type side chain
PHARMACODYNAMICS As for phenothiazine dopaminergic antagonist D2 > 5H T 2 , alpha 1
ABSORPTION Well orally

57% bioavailable due to first pass effect
Half life = 10hours
DISTRIBUTION 80 - 90% plasma protein bound

Vd = 10L / kg
METABOLISM Liver active metabolite - mesoridazine
EXCRETION Faeces 50%

Urine 30%
INDICATIONS Anxiety states / psychiatric disorders / psychosis with anxiety

Senile aggitation and confusional states (dementia)
Organic brain syndrome / intractable pain / childhood schizophrenia
CONTRAINDICATIONS Decreased LO C
Coma
Bone marrow depression
SPECIAL PRECAUTIONS Severe cardiac disease in elderly

Leucopenia - check F BC regularly
Liver dysfunction
INTERACTIONS As for chlorpromazine

Reverse digoxin inotropic effect
Potentiate quinidine
ADVERSE EFFECTS Sedation / postural hypotension marked / lowest extrapyramidal side effects / cardio toxicity
with prolonged QT / flattened T wave / U wave / conduction defects./ pigmentory retinopathy
/ sexual dysfunction / anticholinergics side effects.
DOSING / ADMINISTRATION Anxiety 10-75mg daily. Neuroleptic 50-300mg daily in divided doses maximum 800 mg / day.
Children 1 -4 mg / kg / day in divided doses.
TOXICOLOGY Nausea and vomitting / arrythmia / convulsion / coma / hypotension / circulatory collapse.
Treatment : Moniter / fluids / angiotensin
Dopamine for unresponsive hypotension.
WITHDRAWAL
SYNDROMES
87
t-PA
HISTORY
STRUCTURE/CLASS Recombinant tissue-type plasminogen activator.

Fibrinolytic - recombinant via mammalian cell culture.
PHARMACODYNAMICS Converts plasminogen -- plasmin - fibrin -- FSP.

High affinity for fibrin therefore supposedly activates plasmin in clot- bound fibrin.
Supposedly causes local fibrinolysis >> systemic fibrinolysis.
ABSORPTION IV infusion.
DISTRIBUTION
METABOLISM Cleared via liver metabolism.

In 5 mins plasma level is decreased by 50%/ 10mins by 80%/ 20mins by >90%.
EXCRETION
INDICATIONS 1. Acute myocardial infarction

2. Pulmonary embolism especially indicated if streptokinase
3. Proximal / central DVT contraindicated due to previous exposure.
4. IV canulla de-clotting.
CONTRAINDICATIONS 1. Haemorrhagic diathesis.

2. Recent internal bleeding.
3. Cerebral bleeding - within 2/12 of intracranial / instraspinal surgery.
4. Major operation within 10 days.
5. Uncontrolled hypertension >200/110
6. Infective endocarditis.
7. Acute pancreatitis.
SPECIAL PRECAUTIONS GUSTO trial POSSIBLY indicated in ANTERIOR MI in males (young).

(but ? increased incidence of intracerebral bleeding ??)
INTERACTIONS With oral anticoagulants causing increased bleeding .
ADVERSE EFFECTS Bleeding- may require coagulationfactors and possibly aminocaproic acid.
DOSING / ADMINISTRATION 100mg t-PA over 180 mins:

 10mg in 1-2 mins
 50mg in 1hr
 40mg in 2hrs
TOXICOLOGY
WITHDRAWAL
SYNDROMES
88
Trimethoprim
HISTORY
STRUCTURE/CLASS Trimethoxybenzyl pyrimidine antibiotic.

Weak base - greater activity in acid environment.
PHARMACODYNAMICS Inhibits dihydrofolate reductase of bacteria 50,000 x more effectively than the same enzyme
of mammalian cells.
By doing this - triprim inhibits preferentially bacterial nucleic acid synthesis.
Inhibition of reductase is reversible.
ABSORPTION Absorbed well from the gut.

100% oral bioavailability
DISTRIBUTION Widely distributed to body fluids including CNS.

Lipid soluble. 65 - 70% protein bound.
Vd = 130L / 70 kg
Half life = 11 hours.
METABOLISM Not appreciably metabolized in liver although several metabolites have been identified
EXCRETION 69% excreted unchanged in urine i.e. principal route of excretion is renal
INDICATIONS On its own = U T I treatment.

Can be combined in 1 : 5 (1 part triprim [ 80 mg ] to 5 parts sulfamethoxazole [ 400 mg ])
Combination = cotrimoxazole.
Useful for P.carinii pneumonia / shigella / salmonella and for prostatitis.
CONTRAINDICATIONS If given with sulfamethoxazole - make sure patient is not allergic to sulphonamides
SPECIAL PRECAUTIONS Severe renal impairment.

Serious haematological disorders.
Hepatic parenchymal damage
Pregnancy
Folate deficiency
INTERACTIONS Possible megaloblastic anaemia with high dose pyrimethamine

May increase anti coagulant effect of warfarin
May increase plasma concentrations of phenytoin
Potentiates cyclosporin nephrotoxicity
ADVERSE EFFECTS Minor G I intolerance

Skin rashes / pruritis
Interference with haemopoiesis (rare) - folinic acid reverses this.
DOSING / ADMINISTRATION Triprim PO - 300 mg nocte (adults)

UTI prophylaxis = 100 mg daily (adults)
Cotrimoxazole - 2 tabs bd PO / 3 tabs bd PO in severe infections
TOXICOLOGY Rare = nausea / vomitting / diziness / confusion are the likely symptoms.
Supportive measures usually adequate
Urinary acidification will increase the elimination of triprim. Folate may be required.
WITHDRAWAL
SYNDROMES
89
Valproate
HISTORY First used in France in 1969. Discovered when used as a solvent for other seizure
drugs.
STRUCTURE/CLASS Sodim valproate, free acid is valproic acid. Fully ionised at body pH
A fatty carboxylic acid
PHARMACODYNAMICS Blocks sustained high-frequency repetitive firing of neurons, by:

 Affecting Na+ currents
 Antagonism of (excitatory) NMDA receptors
 Increased GABA levels (mechanism unknown)
ABSORPTION Well-absorbed orally, bioavailability >80%
DISTRIBUTION Highly ionised, highly protein-bound → Distribution essentially confined to

extracellular water
METABOLISM Clearance is low (t½ 9-18h), direct conjugation

Active metabolites
EXCRETION Urine
INDICATIONS 1. Absence seizures; 2. Bipolar disorder; 3. Migraine prophylaxis
CONTRAINDICATIONS Teratogenic, particular ↑ risk of spina bifida (1-2%)
SPECIAL PRECAUTIONS
INTERACTIONS Inhibits its own metabolism at low doses

Displaces phenytoin from plasma proteins
Inhibits metabolism of phenytoin, carbamazepine, phenobarbital → Higher steady-
state concentrations of these agents
ADVERSE EFFECTS GI complaints (nausea, vomiting, heartburn)
Fine tremor at higher levels
Hepatotoxicity, rare but sometimes severe/fatal → Monitoring of liver function when
starting the drug
TOXICOLOGY
90
Vecuronium
HISTORY
STRUCTURE/CLASS Steroid non - depolarising N M blocker
PHARMACODYNAMICS Blocks transmission process between motor nerve ending and striated muscle by binding
competitively with ACh to the nicotinic receptors located in the motor end plate region of
striated muscle.
Works within 90-120 seconds.
ABSORPTION IV
DISTRIBUTION Mainly ECF

Vd = 0.27L / kg in adults
METABOLISM Relatively low rate of metabolism

Plasma clearance approximately 5.2 ml / kg / min
Half life = 71 (+ / - 20 ) mins
Spontaneous reversal
EXCRETION Biliary mainly
Renal low
INDICATIONS For muscle relaxation for intubation.

Safe for CVS patients (is CVS stable) .
Safe for surgery with likely vagal reactions
CONTRAINDICATIONS Former adverse reaction to vecuronium or bromide ion
SPECIAL PRECAUTIONS Administer with full resuscitation facilities by experienced clinician.

Need for intubation
Obese patients - dose according to lean muscle mass.
Care with renal and biliary / hepatic disease - although fairly safe.
Not fully tested in pregnancy/ childbirth
INTERACTIONS Increased effects with anaesthetics / other non-depolarizing agents / prior succinylcholine /
antibiotics / diuretics / beta-blockers / hypothermia
Decreased effects with neostigmine / cortisone / phenytoin / carbamazapine / noradrenaline
/ theophylline / hyperthermia.
ADVERSE EFFECTS Anaphylactic and histaminoid reactions.
DOSING / ADMINISTRATION Intubation dose = 0.08 - 0.10 mg / kg lean mass

Post suxa = 0.03 - 0.05 mg /kg
Maintenance = 0.02 - 0.03 mg/ kg
TOXICOLOGY OD - mechanical ventilation
neostigmine
WITHDRAWAL
SYNDROMES
91
Verapamil
HISTORY Prototype calcium channel blocker.
First introduced as anti-anginal agent.
STRUCTURE/CLASS Calcium channel blocker (result of attempt to synthesize structural analogue of papaverine).
PHARMACODYNAMICS Bind to inner side of calcium channels to decrease trans-membrane calcium current. Blocks
activated and inactivated channels. Results in decreased in cardiac contractility and output.
AV nodal conduction and refractory period are prolonged. Suppresses both delayed and early
depolarization.
Relaxes smooth muscle causing decreased lowered pressure and vascular resistance
ABSORPTION Bioavailability 20-35%

Onset 30mins orally and < 1.5 minsIV.
DISTRIBUTION 90% bound to plasma proteins.
METABOLISM Extensively metabolized by liver.

Plasma half life- = 6 hrs.
EXCRETION Metabolites - 70% eliminated by kidney and 15% by GI tract.
INDICATIONS Angina/ hypertension/re-entrant SVT (except WPW) .

Can reduce ventricular rate in atrial flutter/ fibrillation.
CONTRAINDICATIONS Cardiogenic shock / complicated AMI

2nd and 3rd degree AV block.
Sinus bradycardia and hypotension.
SPECIAL PRECAUTIONS In AF and WPW there is a risk of inducing VT.

AV block
Decreased dose with hepatic dysfunction.
INTERACTIONS Cimetidine/ carbamezepine/ rifampican/ increased metabolism of verapamil.

Verapamil decreass metabolism of cyclosporin and causes increased plasma digoxin levels.
Increased cardiodepressant effects with beta blockers.
ADVERSE EFFECTS Cardiac depression/ cardiac arrest/ bradycardia/ AV block/ CHF/ flushing/oedma/
dizziness/ gingival hyperplasia/ constipation.
DOSING / ADMINISTRATION IV= 5mgover 2-5 mins.

Orally = 120-600 mg daily in divided doses
TOXICOLOGY Extension of clinical effect = cardiac arrest, myocardial insufficincy (treated with dopamine,
dobutamine, glycosides), hypotension.
Use high dose CaCl, consider pacing bypass amrinone
WITHDRAWAL
SYNDROMES
92
Warfarin
HISTORY Spoiled sweet clover silage --- haemorrhagic disease in cattle.
Wisconsin Alumni Research Foundation + arin suffix from coumarin.`
STRUCTURE/CLASS Oral anticoagulant (coumarin).

2 stereoisemers - racemic mixture S-warfarin/ R-warfarin
(4 x as potent)
PHARMACODYNAMICS Inhibits VitK epoxide reductase. VitKO ---VitKH2 (hydroquinone)

VitKH2 required for gamma-carboxylation glutamate residues in ll, Vll, lX, X + protein C
Half life - Vll = 6 hrs. X = 40 hrs. lX = 24 hrs. ll = 60hrs.
ABSORPTION 100% bioavailability.

Usually Na+ salt.
DISTRIBUTION >99% albumin bound therefore Vd = albumin = 0.12L/kg

Therefore long half life of approx.36hrs.
METABOLISM R-warfarin (reduced) / S-warfarin (oxidized) to inactive metabolites by glucuronide

conjugation.
EXCRETION Enterohepatic circulation.

Excreted in urine and stool.
INDICATIONS 1. Rodenticide. 2. Venous thromboembolism.

3. Arterial thrombosis. 4. Atrial fibrillation.
5. Cardiac disease e.g. large anterior MI.
CONTRAINDICATIONS 1. Pregnancy - crosses placenta - haemorrhagic disease in foetus/ abnormal bone formation.
2. Bleeding diathesis.
3. Liver disease.
SPECIAL PRECAUTIONS Need responsible patients.

The following decrease INR - hereditary resistence/ VitK/ hypothyroid/ diuretics
(spironolactone, chlorthlidone) / barbiturates + rifampicin (induce hepatic enzymes) /
cholestyramine (binds warfarin)
The following increase INR - decreased metabolism of S-warfarin by phenylbutazone/
metronidazole / miconazole / trimethoprim/ sulphamethoxazole/ sulfinpyrazone
- decreased metabolism both isomers - amiodarone/ disulfiram / cimetidime.
Aspirin (decreases platelet function) cephalosporins (decrease GI bacteria producing
VitK)
Hepatic disease (decrease clotting factors)
Hypothyroid (decrease survival clotting factors).
INTERACTIONS Other anticoagulants.
ADVERSE EFFECTS 1. Haemorrhage. 2. Tissue Necrosis - venous thrombosis leading to haemorrhagic

infarction secondary to protein C inhibition (cutaneous, breast)
DOSING / ADMINISTRATION 2-5 mg/ day PO until INR therapeutic then stabilize.
TOXICOLOGY Increased INR treat with VitK IV up to 50mg

May use factor concentrates - FFP or factor lX concentrate (with prothrombin)
93
Example Drug Monograph
HISTORY
STRUCTURE/CLASS
PHARMACODYNAMICS
ABSORPTION
DISTRIBUTION
METABOLISM
EXCRETION
INDICATIONS
CONTRAINDICATIONS
SPECIAL PRECAUTIONS
INTERACTIONS
ADVERSE EFFECTS
TOXICOLOGY
94

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Pharmacology - Drug Monographs

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Important drug monographs

Originally from Garry, updated and formatted by Dan

STRUCTURE/CLASS Endogenous nucleoside

ABSORPTION IV with rapid absorption

DISTRIBUTION Most cells

METABOLISM Rapidly degraded by cells:

INDICATIONS 1. SVT 90 - 95% effective conversion

CONTRAINDICATIONS Heart block 2nd or 3rd degree

SPECIAL PRECAUTIONS Patients with asthma.

INTERACTIONS With theophylline it is ineffective - blocks adenoreceptors

ADVERSE EFFECTS Flushing

DOSING/ADMINISTRATION IV - through central line 3-6 mg

TOXICOLOGY Self limiting T½ of 10 seconds

STRUCTURE/CLASS Catecholamine - endogenous Benzene ring + ethyl amine.

ABSORPTION Oral absorption is poor - oxidised and conjugated in gut.

DISTRIBUTION Crosses placenta.

EXCRETION Kidney metabolites inactive.

INDICATIONS 1. Anaphylaxis / allergy -cardiovascular and mast cell effects.

CONTRAINDICATIONS IHD Pheochromocytoma

SPECIAL PRECAUTIONS With local anaesthetic in fingers, toes and ears.

ADVERSE EFFECTS Cerebral haemorrhage. Increased BP.

DOSING / ADMINISTRATION IM / SC / IV or inhaled.

TOXICOLOGY Can be reversed depending on system but VERY short acting.

STRUCTURE/CLASS Potassium sparing diuretic amiloride hydrochloride

DISTRIBUTION Not to be given IV causes hypertension and ECG changes.

METABOLISM Nil in liver.

EXCRETION Excreted 50% in liver unchanged. rest in faeces.

SPECIAL PRECAUTIONS Other forms of K+ supplementation.

INTERACTIONS Decreases clearance lithium.

ADVERSE EFFECTS Minor only - Nausea, anorexia, abdo pain.

DOSING/ADMINISTRATION Oral tablet 5 mg

TOXICOLOGY Rare - supportive measures.

ABSORPTION Depends on formulation. Can be up to 100% orally absorbed.

METABOLISM In liver by demethylation and oxidation.

EXCRETION 10% in urine as unchanged drug.

CONTRAINDICATIONS Uncontrolled arrhythmias, hyperthyroidism, peptic ulcers, uncontrolled seizure disorders.

SPECIAL PRECAUTIONS Peptic ulcer / hyperthyroidism / hypertension / tachyarrhythmias and compromised

TOXICOLOGY Nausea, vomiting, seizures, insomnia, irritability.

STRUCTURE/CLASS Class I, II, III, IV antiarrhythmic.

PHARMACODYNAMICS Blocks inactive Na+ channels (Class I )

ABSORPTION Oral absorption is incomplete and erratic ( individual variability )

DISTRIBUTION Strong protein binding.

METABOLISM Biotransformation to desethylamiodarone - longer half life ( activity unknown)

INDICATIONS Antiarrythmic for supraventricular arrhythmias / ventricular arrhythmias /

SPECIAL PRECAUTIONS Teratogenic.

INTERACTIONS Digoxin - leads to increased digoxin levels.

TOXICOLOGY Supportive measures for hypotension / bradycardia.

STRUCTURE/CLASS Tricyclic antidepressant

DISTRIBUTION 93 - 95 % protein bound. Vd = 14 L / kg Lipophilic - not dialysable.

METABOLISM Liver N - demethylation + ring hydroxylation produce active metabolites.

INDICATIONS Depression (endogenous and reactive ) with sedative effects.

CONTRAINDICATIONS MAOIs -- hypertension / hyperpyrexia / convulsions.

INTERACTIONS Additive anticholinergic effect with antihistamine / Parkinson / psychotic drugs.

ADVERSE EFFECTS CNS - oversedation / confusion / seizure / peripheral neuropathy.

DOSING/ADMINISTRATION PO 75 mg increasing to 150mg. Max = 300 mg/day

ABSORPTION Oral bioavailability = 93% well absorbed from gut.

DISTRIBUTION Distibuted widely through body fluids and tissues.

METABOLISM Half life = 1.7 hrs.

INDICATIONS Broad spectrum antibiotic (inactivated though by beta lactamases)

SPECIAL PRECAUTIONS 1. infectious mononucleosis - rash.

INTERACTIONS 1. Excretion is delayed by probenecid -which blocks tubular secretion.

ADVERSE EFFECTS 1. GI disturbance.

STRUCTURE/CLASS Non catecholamine sympathomimetic agent

ABSORPTION High oral availibility