3 clinical pharmacology

Clinical Pharmacology

Clinical pharmacology • Clinical pharmacology connects the gap between

medical practice and laboratory science.

• The main objective is to promote the safety of prescription, maximise the drug effects and minimise the side effects.

• It is important that there be association with pharmacists skilled in areas of drug information, medication safety and other aspects of pharmacy practice related to clinical pharmacology.

Clinical pharmacology • Clinical pharmacologists usually have a rigorous

medical and scientific training which enables them to evaluate evidence and produce new data through well designed studies

• Their responsibilities to patients include, but are not limited to, analyzingnot limited to, analyzing

– Drug therapeutics, toxicology (including reproductive toxicology), cardiovascular risks, perioperative drug management (those used in operations), psychopharmacology, and Iatrogenic effects (adverse drug effects)

Clinical Pharmacology

• Clinical Pharmacology is the subject of the application of drugs to the body in the medicinal sense

• Drugs can function either by action through • Drugs can function either by action through receptors, or by altering the functions of the target cell/tissue

Principles

of drugs

action

Receptors• One facet of drug action is receptors

– Agonist: do have a stimulatory effect• They produce a response

– Antagonist: do not have a stimulatory effect• They do not produce a response, or have an overall blocking action

for a parallel stimulation

• Types:– Agonist: have a central pore– Agonist: have a central pore– G – Protein: usually linked by secondary messengers to

physiological (cellular) processes – Nuclear receptors for steroid hormones: in cell nucleus

and regulate protein translation and thus synthesis– Kinase – linked receptors: usually process intrinsic tyrosine

activity (insulin, cytokines, growth factors)

Neurotransmitters• These are substances released from the end of

nerve axons, at synapses, and bind to receptors. They activate the receptors, by changing their configuration, and trigger a response in the post-synaptic membrane. If it is an agonist, it may stimulate a muscle contraction or gland secretion.stimulate a muscle contraction or gland secretion.

• After they have produced their effect, they are inactivated by:– Postsynaptic enzymic degradation

– Reabsorption into the pre-synaptic bulb

Hormones• These are chemicals that are released into the bloodstream, then

they act on tissues that have receptors for them (see videos):– Cells a long way away (steroids)– Cells locally– Themselves

• Drug Hormone Actions:– Inhibiting hormone release:

• Antithyroid drugs

– Increasing hormone release:– Increasing hormone release:• Antidiabetic drugs

– Interact with hormone receptors:• Activating: steroidal anti-inflammatory drugs (NSAI)• Blocking: oestrogen antagonists

– Local hormones (released in pathological processes):• Histamine - antihistamine• 5-HT, kinins

• Prostaglandins – aspirin (NSAI)

Synapse - video

Drug-receptor interactions• A drug that has a stimulatory effect is an agonist

• A drug that blocks this activity, or has an inhibitory effect is an antagonist (a term used in relation to the agonist)

• Antagonists can bind in two ways:– Competitive antagonists bind reversibly with receptors; tissue

response can be normalised/increased by increasing the dose of agonist

– Irreversible antagonists bind irreversibly with receptors; their – Irreversible antagonists bind irreversibly with receptors; their effect cannot be reversed by increasing agonist dose

– Others: – Calcium-channel blockers do not via receptors, but further along to

prevent the action of an agonist– Chemical antagonists bind to the active drug, inactivating it e.g.

Protamine abolishes effect of heparin– Physiological antagonists are two agents with opposite effects that

tend to cancel each other out e.g. Prostacyclin and thromboxane- A2 on platelet aggregation

Neuromuscular

junction

ANS

Cholinergic AgonistsDistigmine, Pilocarpine (Pilogel,

Salagen), Pyridostigmine(Mestinon)

EffectsImproves muscular contraction

Uses

• Atonic Bladder and Urinary Retention

Side Effects

• Diaphoresis (sweating)

• Headache

• Urinary Urgency

• Nausea

• Diarrhoea

• Hypotension

• SalivationRetention

– Postpartum or postoperative

• Muscular Weakness

– Myasthenia Gravis

• Ocular Eye Pressure

– Glaucoma

• Flushing

• Abdominal Pain and Cramps

• Bronchial Spasms (panting)

• Heart Palpitations or Tachycardia

• Tremors

Interactions with other conditions

• Asthma, hyperthyroid, hypotension

NMJ blockers• Presynaptic exocytosis (block released of

acetylcholine):

– Botulinum toxin (Botox): blepharospasm, hemifacial spasm (can produce paralysis for about 12 weeks),

wrinkles

– Baclofen (Lioresal) inhibit calcium influx necessary for exocytosis –– Baclofen (Lioresal) inhibit calcium influx necessary for exocytosis –

usually only NMJ blockers

– Aminoglycoside antibiotics: inhibit calcium influx necessary for

exocytosis – usually only NMJ blockers

– Dantrolene (Dantrium) -Chronic spasticity

Competitive NMJ blockers• Block nicotinic receptors: used by anaesthetists to relax skeletal

muscle during ECT; usually given IV and don’t pass BBB or placenta. The drug of choice depends upon the side-effects– Includes:

• Histamine release• Vagal blockade • Ganglion blockade• Sympathomimetic

• Curare (introd 1942; not longer used)• Curare (introd 1942; not longer used)• Gallamine – doesn’t block ganglia, or releases histamine, but causes tachycardia

• Pancuronium – an aminosteroid and blocks muscarinic receptors, causing atropine-like tachycardia

• Vecuronium and atracurium – commonly used without CVS effect (only stable when kept cold at low pH, so in body its breakdown does not depend upon renal/hepatic function, so good for patients with those problems

Depolarising NMJ blocking drugs• Suxamethonium (Anectine)– depolarises the

post-synaptic membrane; initiates brief contractions, then the block occurs because:– Inactivation of the voltage sensitive Na channels

– Transforms activated receptors to a ‘desensitised state’ and unresponsive to ACh. state’ and unresponsive to ACh.

• Disadvantages:– Initial muscle RXN may cause damage - pain

– Damage causes K release

– Repeated doses may cause bradycardia in absence of atropine

Potentiating drugs of NMJ• Neuromuscular transmission can be increased by

anticholinesterases

• They block the break down of acetylcholine and thus maintain, or potentiate, the effects of nerve stimulation

• Effective in conditions like myasthenia gravis; an autoimmune condition with antibodies autoimmune condition with antibodies competing for receptors– Neostigmine

– Pyridostigmine (Mestinon)• Dosage needs to be accurate; overdose can cause xs Ach and a

depolarising block of the NMJ

Acetylcholinesterase Inhibitors

e.g. Donepezil (Aricept), Rivastigmine (Excelon), Pyridostigmine (Mestinon), Neostigmine, Galantamine

Uses

• Cognitive Deficit

Side Effects

• As Cholinergic Agonists

Interactions with other

conditions– Alzheimers

• Attention Deficit (impaired memory)– ADHD

• Muscular weakness – Myasthenia Gravis

conditions

• Constipation

ANS

ANS

ANS

Drugs acting at cholinergic synapses

• Muscarinic agonists– Carbechol– Pilocarpine (Salagen)– Bethanechol

• Anticholinesterases– Edrophonium– Neostigmine– Distigmine

• Nicotinic agonists (ganglion stimulants)

– Nicotine– Carbechol (weak)– Anticholinesterases (weak)

• Ganglion blockers– Trimetaphan– Xs nicotine (depolarising block)– Distigmine

– Pyridostigmine– (organophosphorus

compounds)

– Xs nicotine (depolarising block)

• Muscarinic antagonists– Atropine– Hyoscine– Ipratropium– Tropicamide– Benzatropine– Others

Antimuscarinic Agents – muscarinic blockersAtropine (Atropine), Benzatropine,

Biperiden, Dicycloverine/Dicyclomine (Merbentyl), Homatropine, Hyoscine (Buscopan), Oxybutynin (Cystrin, Ditropan), Orphenadrine (Biorphen, Disipal), Procyclidine (Arpicolin, Kemadrin), Tolterodine (Detrusitol), Trihexyphenidyl, Trospium

Others : Ipratropium Bromide (Atrovent, Combivent, Respontin), Oxitropium,

• Side Effects

– Blurred vision

– Confusion

– Drowsiness

– Dizziness/Vertigo

– Constipation

– Dry Mouth

– Palpitations - TachycardiaCombivent, Respontin), Oxitropium, Tiotropium (Spiriva), Baclofen (Baclospas, Balgifen, Lioresal), Carisprodol, Dantrolene, Methocarbamol

Uses

• GI Tract, Bladder spasms – Irritable Bowel, Abdominal Pain, Incontinence

• Muscle Rigidity and Spasms –Parkinsons

• Bronchodilators – Asthma

– Palpitations - Tachycardia

– Restlessness

– Headache

– Urinary Retention

Drugs

acting at

cholinergic

synapses

Adrenaline Effects Biological advantage Sensation

High heart beat Sends more glucose & oxygen to

the muscles

Thumping heart

High respiratory rate Increased oxygenation of the

blood; rapid removal of carbon

dioxide

Panting

Arteriole constriction Blood diverted from skin &

digestive system to muscles

Person turns pale

digestive system to muscles

Muscle tension Ready for immediate action Tense feeling; Shivering; Erect

body hair

Glycogen is converted to

glucose

Glucose available for energy

production

Fats are converted to

fatty acids

Muscles contraction

ANS- Adrenoceptors

• Adrenoceptors: - two main types: α, β

– α: 2 types:

• α1 – vasoconstriction

• α2 –– inhibition of insulin release in pancreas

induction of glucagon release from pancreas. – induction of glucagon release from pancreas.

– contraction of sphincters of the gastrointestinal tract

– negative feedback in the neuronal synapses

– platelet aggregation

ANS- Adrenoceptors

– β:- 2 types:

– β1 –

• Increase cardiac output

• raising heart rate (positive chronotropic effect)

• increasing impulse conduction• increasing impulse conduction

• increasing contraction thus increasing the volume expelled with each beat (positive inotropic effect; increased ejection fraction).

• Renin release from juxtaglomerular cells

• Lipolysis in adipose tissue

ANS- Adrenoceptors• β2 -

– Smooth muscle relaxation, e.g. in bronchi– Lipolysis in adipose tissue– Anabolism in skeletal muscle – Relax non-pregnant uterus – Relaxes detrussor muscle of bladder wall – Dilate arteries to skeletal muscle – Dilate arteries to skeletal muscle – Glycogenolysis and gluconeogenesis – Contract sphincters of GI tract – Thickened secretions from salivary glands – Inhibit histamine-release from mast cells – Increase renin secretion from kidney – Promotes insulin release from pancreatic beta cells

Drugs acting on sympathetic systemSympathomimetics• Indirectly acting

– Ephedrine– Amphetamine– Cocaine

• Directly acting

– α- agonists

– α1, α2• Noradrenalin• Adrenaline

– α2

• Adrenergic neurone blockers– Reserpine– Guanethidine– Bethanidine

• Adrenoceptor antagonists– α – Blockers

– α1, α2• Phenoxybenzamine• Phentolamine– α2

• Clonidine (Catapress)

• α-methyl-noradrenalin

– α1 • Phenylephrine• Metaraminol

• Phentolamine– α1

• Prazosin (Hypovase)• Doxazosin (Cardura)• Guanethidine• Prazosin• Terazosin• Tamsulosin (Flomax)

Drugs acting on sympathetic system

Sympathomimetics

• Indirectly acting

– Ephedrine

– Amphetamine

– Cocaine,

– Methamphetamine

– Dex(tro)amphetamine

– Methylphenidate (Ritalin)

Side Effects

• Diaphoresis (sweating)

• Headache

• Palpitations

• Fatigue

• Angina

• Depression

• Hypotension

• Hypertension

• Dry Mouth– Methylphenidate (Ritalin)

– Modafinil

– Uses

– Obesity

– Somnolence

– ADHD

– Sleep Apnea

– Fatigue

– Recreational Drugs

• Dry Mouth

• Nausea and Vomiting

• Poor Appetite

• Diarrhoea

• Abdominal Cramps

• Overdose – restless, irritable, insomnia, dizziness, tremors, talkative, fever, anxiety, panic, confusion, delirium, hallucinations, aggressiveness, psychosis, suicidal/homicidal thoughts, convulsions, coma, cerebral haemorrhage

• These drugs should not be used

concurrently with MAOI’s

Adrenergic (alpha) blockers

• Doxazosin (Cardura), Guanethidine, Prazosin, Terazosin, Tamsulosin(Flomax), Bethanidine, Phenoxybenzamine, Phentolamine

• Uses

– Hypertension

Side Effects

• Postural Hypotension

• Nausea and Vomiting

• Nasal Congestion

• Fatigue

• Headache

• Poor Ejaculation– Hypertension

– Prostatic Hypertrophy

– Relieves constriction of Bladder and Prostrate sphincters

• Poor Ejaculation

• Palpitations - Tachycardia

• Oedema

Adrenergic β agonists

– β- agonists

– β1, β2• Adrenaline

• Isoprenaline

– β2• Salbutamol

• Terbutaline

– β- blockers

– β1, β2

• Propranolol (Inderal)

• Timolol (Moducren)

– β1 (cardioselective)

• Metoprolol (Betaloc, • Terbutaline

– β1• Noradrenalin

• Dobutamine

• Metoprolol (Betaloc,

Lopressor)

• Atenolol (Atecor)

Adrenergic β agonists

Adrenaline, Isoprenaline, Salbutamol, Terbutaline, Noradrenalin, Dobutamine, Xamoterol

Uses

• Congestive Heart failure

• Bradycardia

Side effects

• Tachycardia

• Arrhythmias

• Hypertension

• Angina

• Bradycardia

• Asthma

• Anaphylaxis

Drugs acting

on

sympathetic

system

Managing hypertension• Usually done with a combination of factors;

– Blood pressure reduction

– Diuretics

– Cholesterol

– Anxiety– Anxiety

Blood pressure

Drug groups used to control blood pressure:

• β Blockers

• Diuretics

• Calcium channel blockers

• Angiotensin converting enzyme (ACE) inhibitors

• Angiotensin II receptor blockers (ARBS)• Angiotensin II receptor blockers (ARBS)

There is no reliable/consistent evidence indicating substantive differences between drugs classes in the effects on BP, but side effects profiles of each drug class differ.

Beta Blockers

Atenolol (Antipressan, Beta Adalat, Tenormin, Tenoret), Betaxolol, Bisoprolol, Celiprolol, Esmolol, Metoprolol (Betaloc, Lopresor), Nebivolol (Nebilet), Acebutolol, Carvedilol, Labetalol, Nadolol, Pindolol, Propranolol (Cardinol,Inderal), Sotalol(BetaCardone,Sotacor), Timolol (Betim, Prestim, Timoptol)

Action - Cardiac Selective and Non Cardiac Selective.

• Beta blockers counteract the action of noradrenalin, and reduce the force and

Side Effects

• Heart Palpitations – Bradycardia

• Hypoglycaemia (reduced glycogenolysis)

• Bronchoconstriction

• Insomnia

• Nightmares

• Depression, Fatigue

• Cold Extremities

• Peripheral Vascular Disease

• Reynaud's Syndromenoradrenalin, and reduce the force and speed of the heart beat. Non Cardiac Selective drugs also prevent dilation of blood vessels in the head and extremities.

Uses

• Hypertension

• Migraines

• Hyperthyroidism

• Angina

• Myocardial Infarction

• Reynaud's Syndrome

• Decreased Libido and Ejaculation Problems

Contraindications

• Bradycardia

• Hypotension

• Metabolic acidosis

• Peripheral arterial disease

• Heart block/failure

• Phaeochromocytosis

• Bronchial asthma

Diuretics• Aldactide, aldactone, Centyl,

dyazide, fruside, lasix, moduret, natrilix, napamide, natrilix,

Actions

• Reduce volume in cardiovascular system

Uses

• Hypertension

Side effects

• Headaches

• Dizziness

• Fatigue

• Urinary tract obstruction

• Postural hypotension

• GIT disorders

• Electrolyte disturbances• Electrolyte disturbances

• Polyuria

• Muscle cramps

• Tinnitus

Calcium channel blockers

• Nifedipine (adalat), Diltiazem(adizem), amlid, amlist, amlode, amlotan, diltam-retard, dilzem, entrydil, exforge, myostin, nifed, nivadil, plendil, rustin, tildiem, triapin, tritace, verap, verisop, zanidip,

Actions

Side effects

• Ankle swelling

• Headache

• Flushing

• Palpitation

• Nausea/dyspepsiaActions

• Presynaptic neurone blocker

Uses

• hypertension

• Nausea/dyspepsia

• Abdominal pain

• Dizziness

• Lethargy

ACE inhibitors

• Accupro, accuretic, aceomel, bitrite, capoten, captor, carace, coversil-arginine, cozaar, enap, geroten, gopten, innovace, lisopress, lispril, loavel, odrik, pendrex, ramic, ramilo, ramitace, vascace, zesger, zestan, zestril, zofenil

Actions

Side effects

• Headache

• Dizziness

• Rhinitis/cough

• Upper respiratory tract infection

• Fatigue

• Nausea

• DyspepsiaActions

Inhibits conversion of angiotensin I to angiotensin II

Uses

• Hypertension

• Dyspepsia

• Myalgia

• Chest/abdominal pain

• Hypotension

• Angioedema

Angiotensin II blockers

• Aprovel, atacand, benetor, beta-adalat, diovan, isoptin, istin, micardis, omesar, teveten,

Actions

• Side effects

• Chest/back/abdominal pain

• Arthralgia

• Fatigue

• Dyspepsia• Causes vasodilatation,

blocks vasopressin release

Uses

• Hypertension

• Dyspepsia

• Rhinitis/pharyngitis

• Dyspnoea

• Upper RTI/viral

• Headache

• Dizziness

Antihypertensive

drugs

Angina Drugs

• Short acting nitrates

– Glyceryl trinitrate (Glytrin, Nitrolingual)

• Long acting nitrates

– Isosorbide (Elantan, Imdur, Isomel)

• Calcium antagonists• Calcium antagonists

– Nifedipine (Adalat, Nifed)

– Amiodipine (Amid, Amiotan)

Cardiac Arrhythmias • Anti-Arrhythmics

Sodium Channel Blockers: Disopyramide, Flecainide, Phenytoin (Epanutin), Procainamide, Propafenone, Quinidine

Potassium Channel Blockers:

• Amiodarone (Cordarone), Sotalol(Beta Cardone, Sotacor)

• (Also Beta Blockers, Calcium Channel

Side Effects

• Potential exacerbation of arrhythmias

• Flecainide, Propafenone – Dizziness, blurred vision, headache, nausea, ventricular tachycardia

• Amiodarone – interstitial pulmonary fibrosis, tremors, ataxias, dizziness, thyroid and liver disease, photosensitivity, muscle weakness, neuropathy

• Disopyramide, Quinidine – dry mouth, urinary retention, blurred vision,

• (Also Beta Blockers, Calcium Channel Blockers, Inotropic Agents – see sections)

Uses

• Arrhythmias e.g. atrial fibrillation or flutter, ventricular fibrillation, atrioventricular blocks, sinus arrhythmias, Palpitations –Bradycardia, Tachycardia

• Impulse tramissions from other than the sinoatrial node – e.g. potassium imbalance in other cardiac cells

urinary retention, blurred vision, constipation

• Quinidine – may cause SA or AV node block, ventricular tachycardia, nausea, vomiting and diarrhoea, blurred vision, tinnitus, headache, disorientation, psychosis

• Procainimide – erythema, ventricular arrhythmias, depression, hallucination, psychosis

Heart failure • Inotropic agents

– Digoxin

– Dobutamine

• β- Blockers

– Carvedilol (Eucardic)

– Bisoprolol (Cardicor)

• Diuretics

– Bendroflumethiazide (Centyl K)

– Bumetanide (Burinex)

– Furosemide (Frumil)

• Aldosterone antagonist– Bisoprolol (Cardicor)

– Metoprolol (Betaloc)

• Aldosterone antagonist

– Spironolactone (Aldactide)

• ACE inhibitors

– Captopril (Capoten)

– Enalapril (Innovace)

Cholesterol reducing drugs (Statins)

• Atorvastatin (Lipitor), Fluvastatin, Lovastatin, Pravastatin (Lipostat), Rosuvastatin (Crestor), Simvastatin (Vytorin, Zocor)

Action

• Reduce LDL and VLDL Cholesterol by inhibiting HMG-CoA enzyme used to produce cholesterol in the Liver, and so reduce release

Side Effects

• Muscle Cramps

• Abnormal Liver Function Tests

• Steatosis (Fatty Liver)

• Pancreatitis, Hepatitis, Jaundice

• NAFLD (Non Alcoholic Fatty Liver Disease)

• NASH (Non Alcoholic Steatotic Hepititis)

• Cirrhosis

• Muscle Wastage – Rhabdomylosis (raised serum creatine ->urine)

• Acute Kidney Failure (peripheral oedema, weight gain, poor appetite,

the Liver, and so reduce release into the Bloodstream.

Uses

• Hyperlipidemia (High Cholesterol)

Also

• Cholesterol absorption inhibition

– Ezetimibe (Ezetrol)- used in combination with statins

weight gain, poor appetite,

• weakness, nausea)

Precautions

• Not to be used with concurrent Liver Disease or the Oral contraceptive. Liver function tests must be performed before administration and repeated regularly during treatment. CreatinePhosphokinase (CPK) levels should be performed in anyone with kidney impairment, hypothyroid disorder, inherited muscle disorders, previous muscle toxicity in conjunction with statin use or alchohol abuse

Fibrates/Bile Sequestrants/Lipase Inhibitors

• (Questran), Colestipol, Ezetimibe(Vytorin, Zetia), Niacin (Advicor, Niacor,Niaspan), Omega 3 Acid Ethyl Esters (Omacor), Orlistat(Zenical)

Bile Acid Sequestrants bind with bile acids and salts from the GallBladder in the SI and cause their excretion. The Liver then

Ezetimibe inhibits cholesterol absorption from the gut. Again the Liver responds by increasing LDL uptake from the blood.

Niacin acts on adipose tissue and blocks formation of fatty acids to circulate in the blood to the Liver for repackaging into LDL.

Uses

• Hyperlipidemia (High Cholesterol)their excretion. The Liver then takes up more LDL from the blood to compensate for lack of dietary input, and also causes increased bile acid production to take more cholesterol from the gut.

Fibrates cause an increase in lipoprotein lipase which breaks down VLDL and promotes storage of fatty acids in adipose and other tissues.

• Hyperlipidemia (High Cholesterol)

Side Effects

• BAS – Nausea, Flatulence, Constipation, interferes with absorption of fat soluble vitamins A D E and K

• Fibrates – cholelithiasis, muscle inflammation and pain and muscular weakness

• Niacin – skin flushing, burning and itching, nausea, abdominal pain, hyperuricemia, and gout

Lipid lowering

drugs

Blood coagulation – DVT etc• Anticoagulants:

– Vitamin K antagonist• Warfarin (Warfant)

– Heparin– DVT, CVA, MI

– Bemiparin (Zibor)

– Enoxaparin (Clexane)

• Anti-platelet:

– Aspirin– Angina, MI

– Clopidogrel (Plavix) if aspirin C/I

– Tirofiban (Agrastat)

– Eptifibatide (Integrillin)– Enoxaparin (Clexane)

• Fibrinolytics:• Myocardial infarction

– Streptokinase

– Alteplase (Actilyse)

– Reteplase (Rapilysin)

– Eptifibatide (Integrillin)

– Abciximab (Reopro)

– Dipyramidole (Persantin)– Prosthetic heart valves

Anticoagulants • Abciximab, Aspirin (Caprin, Disprin,

Nuseal, Anadin), Clopidogrel (Plavix), Dipyridamole (Persantin, Asasantin), Eptifibatide, Ticlopidine, Tirofiban

• Other : Warfarin (Marevan, Coumadin)

Actions

• Prevent platelet aggregation and coagulation reactions - venous thrombosis, pulmonary embolism

Side Effects

• Prolong bleeding times: Haemorrhage, GI Bleeding, Thrombocytopenic Purpura

• Warfarin – pain and swelling, headaches, dizziness, weakness, unusual bruising, nose thrombosis, pulmonary embolism

and thrombo embolisms.

Uses

• Angina

• Myocardial Infarction

• Prevention of cardiovascular occlusion – DVT/embolism

• Transient Ischemic Attacks (TIA’s)

unusual bruising, nose bleeds, bleeding gums, heavy menstrual bleeding, brown or pink urine, red or black stools, coughing or vomiting blood

Drugs affecting blood

coagulation

Agents used in anaemia

• Fe preparation (increases Fe available)– Oral:

• Ferrous sulphate

• Ferrous gluconate

• Ferrous fumarate

– Parenteral • Iron dextran (ferric hydroxide)

• Iron sucrose (ferric hydroxide)

• Vitamins (important for normal blood production)– B12, B9 (folate)

• Erythropoietin (produced by the peritubular capillary endothelial cells in the kidney; stimulates erythropoiesis in bone marrow - If renal failure)

Agents used in anaemia

Ocular pharmacology

• Glaucomaβ – Blockers (reduce aqueous humour production)

• Betaxolol (Betoptic)• Cartelol (Teoptic)• Timolol (Nyogel)

Prostaglandin analogues (increase uveoscleral outflow)• Latanoprost (Xalatan)

• Bimatoprost (Ganfort)

Carbonic anhydrase inhibitors (reduce aqueous humour production)• Acetazolomide• Acetazolomide• Dorzolamide• Brinzolamide

Sympathomimetic (reduces production aqueous humour and outflow) • Adrenaline, guanethidine (Ganda)• Brimonidine (Alphagan)

• Age related macular degeneration– Verteporfin (Visudyne)

Ocular

pharmacology

COPD (asthma/bronchitis/emphysema/cystic fibrosis etc)

• Bronchodilators –(COPD) (Relievers)

– β2 agonists• Salbutamol (Ventolin)

• Terbutaline (Bricanyl)

– Muscarinic blockers• Ipratropium (Atrovent)

Side effects (brochodilators)

• Tremor

• Tachycardia

• Headache

• Hypokalaemia

• Steroids (Preventers)

– Beclomethasone (Becotide)

– Serotide (salmetrol and • Ipratropium (Atrovent)

– Combinations• Salbutamol, Ipratropium

(Combivent)

– Xanthines• Aminophylline

(Phyllocontin)

– Serotide (salmetrol and fluticasone)

Side effects

• Hoarseness

• Candidiasis of mouth

Hay fever (rhinitis) and AnaphylaxisAntihistamines:

Non-sedating - Acrivastine, Cetirizine(Benadryl, Piriteze), (Des)Loratidine(Clarityn), Fexofenadine, Levocetirizine, Mizolastine

Sedating – Alimemazine, Azatadine, Brompheniramine, Chlorphenamine(Piriton, Contac 400, Tixylix), Cinnarizine(Cinaziere, Stugeron), Clemastine, Cyclizine, Diphenhydromine, Diphenylpyraline, Hydroxyzine, Meclozine, Promethazine (Phenergan, Sominex, Night

Side Effects

• Fatigue

• Drowsiness

• Sedation

• Hypotension

• Dry mouth and eyes

• Palpitations – Tachycardia

• Vertigo

• Hunger

• Urinary RetentionPromethazine (Phenergan, Sominex, Night Nurse, Pamergan, Tixylix Night Time), Triprolidine

• Sodium Chromoglycate (Intal)

– Mast cell stabiliser; reduces histamine release in allergic asthma

Uses

• Allergic Rhinitis

• Dry out mucous membranes

• Motion Sickness

• Insomnia

• Urinary Retention

Overdose

• Hallucinations

• Convulsions

• Ataxia

• Coma

• respiratory and cardiac collapse

Asthma hay fever and

Anaphylaxis

Drugs on GIT 1

Antacids– NaHCO3– CaCO3– Mg(OH)2– Al(OH)3

Acid secretion reducers– Proton pump inhibitors

– Lanzoprazole (Zoton)– Omeprazole (Losec)– H2 anatogonists

– Cimetidine (Cedine)– Rantidine (Zantac)– Famotidine– Nizatidine– Esomaprazole

• Helicobacter pylori eradication – Triple therapy

• Omeprazole (Losec)• Clarythromycin (Klacid)• Amoxicillin (Amoxil)• Omeprazole (Losec)• Amoxicillin (Amoxil)• Metronidazole (Flagyl)

Side effects

• Nausea• Diarrhoea• Headache

– Esomaprazole

Mucosal strenghteners

• Sucralfate (Antepsin)• Bismuth chelate• Misoprostal (Cytotec)

Uses

• Reduces secretion of Gastric Acid• Peptic Ulcers• Duodenal Ulcers• Gastro-oesophogeal Reflux

• Headache• Dizziness• Muscle Pain• Uterine Contractions

Drugs on GIT 1 –

peptic ulcer

Drugs on GIT 2 – motility and secretions• Crohn's disease, ulcerative colitis

• Anti-inflammatory

– Corticosteroids

• Hydrocortisone

• Prednisolone (Predenama)

– Aminosalicylates

• Sulphasalazine

• Mesalazine (Asacolon, Mezavant)

• Laxatives

– Bulk

• Bran

• Ispaghula (Fibrogel)

• Gallstone dissolvers– Bile acids

• Ursodeoxycholic acid• Antispasmodics (smooth M relaxants)

– Muscarinic agonists• Alverine (Spasmonal)

• Mebeverine (Colofac)

• Peppermint oil (Colpermin)

• Antimotility drugs (Poss with rehydration)– Morphine-like agents

• Morphine• Codeine– Osmotic

• MgSO4

• Lactulose

– Stimulant

• Senna

• Bisacodyl (Dulcolax)

• Co-Danthromer (Codalax)

• Glycerol (suppositories)

– Faecal softeners

• Docusate

• Arachis oil (enema)

• Codeine• Diphenoxylate, Atropine

(Lomotil)

• Loperaminde (Imodium)

• Motility stimulants (DA agonists)– Metoclopramide– Domperidone

• Pancreatic supplements– Pancreatin (Nutrizyme)

Diarrhoea

• Diphenoxylate (Lomotil), Kaolin, Loperamide (Diocalm, Imodium, Diareze, Arret), Methylcellulose (Celevac)

Actions

• Opioid drugs to decrease muscle propulsion in the bowel by working on local opioid receptors in the bowel and slow the

Side Effects

• Abdominal Distension and Cramps

• Flatulence

• Bloating

• Constipation

• Fatigue

• Drowsinessin the bowel and slow the intestines. Bulk forming agents absorb water and irritants in the bowel and produce larger and firmer stools.

Uses

• Diarrhoea

• Drowsiness

• Dizziness

• Itching

• Rashes

• Dry Mouth

Precautions

• Not to used in cases of colitis

• Can affect absorption of other drugs

Constipation

• Bisacodyl, Glycerol, Senna, Sodium Picosulfate, Lactulose (Duphalac, Regulose), Magnesium Citrate, Magnesium Hydroxide (Milk of Magnesia, Maalox, Mucogel), Magnesium Sulphate, Polyethylene Glycol (Liquid Paraffin) (Glycolax)

Actions

• Stimulants irritate the GI tract and increase peristalsis for directly

Also

• Bulk

– Bran

– Ispaghula (Fibrogel)

• Osmotic

– MgSO4

– Lactulose

• Stimulant

– Senna

– Bisacodyl (Dulcolax)

– Co-Danthromer (Codalax)

– Glycerol (suppositories)

• Faecal softenersincrease peristalsis for directly stimulate colon activity. Softening agents emulsify the stool. Osmotic laxatives cause water to stay in the intestines

Uses

• Constipation

• Faecal softeners

– Docusate

– Arachis oil (enema)

Side Effects

• Flatulence

• Belching

• Stomach and Abdominal Cramps

• Diarrhoea

• Nausea

• Abdominal Distension

• Osmotic laxatives can cause electrolyte imbalances

Irritable bowel disease/syndrome

• Aminosalicylates : Balsalazide, Mesalazine (Asacol, Pentasa, Salofalk), Olsalazine (Dipentum), Sulfasalazine (Salazopyrin, Sulazine, Ucine)

Actions

• These drugs block production of prostaglandins and other chemicals that promote inflammation in the bowel

Side Effects

• Nausea and Vomiting

• Malaise

• Poor Appetite

• Diarrhoea

• Headaches

• Abdominal Pain

• Joint Pain

• Tinnitis

• Insomnia

• Fatigue

• Feverinflammation in the bowel

Uses

• Ulcerative Colitis

• Crohn’s disease

• Fever

• Rash

• Sore Throat

• Haemmorhage

• Erythema Nodosum

• Hypertension

• Palpitations

• Pancreatitis

• Liver problems

Drugs on

GIT 2 –

motility and

secretions

Drugs acting on kidney - Diuretics

• Thiazides (distal tubule, inhibits

Na reabsorption)

– Bendroflumethiazide(Centyl)

– Indapamide (Natrillix)

• Loop agents (inhibit Na/K/Cl

reabsorption in ascending loop of Henle, so no water)

• Carbonic anhydraseinhibitors (weak – rarely used)

– Acetazolamide

• Aldosterone

• Potassium sparing diuretics (act on distal nephron; reabsorption in ascending loop of Henle,

so no water)

– Furosemide (Lasix)

– Butemamide (Burinex)

diuretics (act on distal nephron;

reduces Na reabsorption, so spares K)

– Spironolactone(Aldactone)

– Amiloride

– Triametarene

Drugs acting on kidney - Diuretics• Thiazides

– Bendoflumethiazide (Inderex, Inderetic, Prestim), Chlorthalidone, Cyclopenthiazide, Hydrochlorothiazide (Acezide, Capozide, Co-Betaloc, Dyazide, Moduretic), Indapamide(Natrilix, Coversyl Plus), Metolazone, Xipamide

Action

• Inhibit the Na+ transporters in the proximal and distal tubules, which allows more water to stay in the tubules. These diuretics loose efficiency with decreased kidney function. They cause loss of potassium and magnesium, and cause

Side Effects

• Thiazides/Loop Diuretics

• Hyponatremia – lethargy, muscle cramps, dizziness, hypotension, confusion, palpitations, fainting

• Hypokalemia – diet (bananas, citrus fruits, prunes) - Muscle weakness, fatigue, dizziness, confusion, cardiac arrhythmias, constipation

• Hyperuricemia – goutpotassium and magnesium, and cause increased calcium reabsorption.

Uses - broad

• Premenstrual Oedema (severe)

• Oedema

• Ascites

• Congestive Heart Failure

• Nephrotic Syndrome

• Hyperuricemia – gout

• Hyperlipidemia – high cholesterol

• Hyperglycemia – increased blood sugar (danger for diabetics)

Precautions

• Can decrease effectiveness of anticoagulants

• Can’t be used with low potassium, cirrhosis, Addison’s or with Lithium

Drugs acting on kidney - Diuretics

• Loop Diuretics

– Bumetanide (Burinex), Furosemide/Frusemide(Co-Amilofruse, Lasix, Frusol, Frumil, Lasikal), Torasemide

Actions

• Loop diuretics work in the Loop of Henle(which accounts for 25-30% of all NaCLreabsorption) again inhbiting the Na+ transporters. They cause loss of potassium and magnesium but leave calcium levels unchanged.

Uses

Side effects

• Hyponatremia – lethargy, muscle cramps, dizziness, hypotension, confusion, palpitations, fainting

• Hypokalemia – diet (bananas, citrus fruits, prunes) - Muscle weakness, fatigue, dizziness, confusion, cardiac arrhythmias, constipation

Uses

• Pulmonary Oedema

• Hyperkalemia

• Hypercalcemia

Broad uses

• Premenstrual Oedema (severe)

• Oedema

• Ascites

• Congestive Heart Failure

• Nephrotic Syndrome

• Hyperuricemia – gout

• Hyperlipidemia – high cholesterol

• Hyperglycemia – increased blood sugar (danger for diabetics)

Drugs acting on kidney - Diuretics• Potassium Sparing

– Amiloride (Amilamont, Amilospare, Burinex, Co-Amilofruse, Moduretic), Spironolactone, Triamterene (Dytac, Dyazide, Frusene, Triamax, Kalspare)

Actions

• Potassium sparing diuretics work in the collecting tubule and inhibit Na+ reabsorption there as with other diuretics but also prevent potassium excretion. They are not strong diuretics but are often

Side effects

• Peptic ulcers

• Infertility – sperm and egg abnormalities

• Nausea

• Lethargy

• Confusion

• Leg Cramps

• Increased Blood Urea NitrogenThey are not strong diuretics but are often used alongside others to prevent potassium loss.

Uses

• Premenstrual Oedema (severe)

• Oedema

• Ascites

• Congestive Heart Failure

• Nephrotic Syndrome

• Increased Blood Urea Nitrogen

• Increased Uric Acid

• Hyperlipidemia

• Hyperkalemia – tiredness, confusion, muscle weakness, irregular pulse, muscular paralysis, cardiac arrhythmias, cardiac arrest.

Drugs

acting on

kidney -

Diuretics

Central transmitter substancesFast point to point signalling

• Acetylcholine (nicotinic effects)• Amino acids

– Glutamate (excitatory)

– Aspartate– GABA (inhibitory)

– Glycine

Slow, regulatory, signals

• Neuropeptides (over 40 of these)

– Substance P– Met-enkephalin– Leu-enkephalin– Angiotensin– Somatostatin– LH releasing H– Calcitonin gene-related peptide (CGRP)– Others

• Monoamines Monoamines – Dopamine– Nor-adrenalin– Adrenalin– Serotonin (5HT)– Acetylcholine (ACh)

excitatory/muscarinic. Loss of cholinergic pathways important in Alzheimer's

• Donezepil• Rivastigmine

• Nitric oxide

Central transmitter

substances

Antiepileptic drugs

Antiepileptic drugs

• Generalised (tonic-clonic) and partial seizures – Carbamazepine (Tegretol)

– Valproate (Epilim)

– Phenytoin (Epanutin)

– Lamotrigine (Lamictal,

Lamoro)

– Topiramate (Topamax)

• Status epilepticus iv– Lorazepam (Ativan)

– Diazepam (Valium, Anxicalm)

– Phenytoin (Epanutin)

• General anaesthetics

– Propofol (Diprivan)

– Thiopental

Absences – Topiramate (Topamax)

– Phenobarbital (also sedative)

– ‘Add ons’ if epilepsy not controlled:

– Vigabatrin (Sabril)

– Gabapentin (Neurontin,

Gabin)

– Tiagabine (Gabitril)

• Absences – Ethosuximide

– Valproate (Epilim)

• Grand mal and absences– Valproate (Epilim)

– BDZ: Clonazepam (Rovotril)

Drugs for Parkinson’s Disease• Aetiology

– Mostly unknown

– Toxin induced (via MPTP, Carbon monoxide, Manganese)

– Drug induced• Neuroleptics

• Dopamine antagonists

• Antimuscarinic drugs

– Muscarinic antagonists

• Benzatropine

• COMT inhibitor– Entacapone (Comptess)

• Dopaminergic drugs:– DA precursor

• Levidopa (Madopar)

• (+Carbidopa (Sinemet) or Benserazide)

– Releases DAAmantadine (Symmatrel)• Benzatropine

• Procyclidine (Kemadrin)

• Orphenadrine

• MAO inhibitors

– Selegiline (Eldepryl)

• Amantadine (Symmatrel)

– DA agonists/ergot derivatives• Bromocriptine (Parlodel)

• Carbergoline (Carbaser, Dostinex)

• Pergolide (Celance)

– Non-ergot derivatives• Ropinirole (Adartrel, Requip)

• Pramipexole (Mirapexin)

Parkinson’s Drugs

• Entacapone (COMT), Amantadine(Symmetrel), Bromocriptine(Parlodel), Cabergoline, Lisuride, Pergolide, Pramipexole (Mirapex), Ropinirole (Requip), Levodopa/Carbidopa (Sinemet)

COMT (catechol-O-methyl

transferase) Inhibitor – inhibits enzyme that breaks down

Side Effects

• Hallucinations (Visual, Auditory)

• Dyskinesias (too much activation of CNS)

Also:

• Levodopa/COMT - Tachycardia, hypotension, brown urine, anxiety, depression, poor appetite, nausea, vomiting

enzyme that breaks down Dopamine and Levodopa

Dopamine Receptor Agonists –activate Dopamine receptors artificially instead of Dopamine. The mechanism of action of Amantadine (an antiviral agent against Influenza A) is unknown.

Levodopa/Carbidopa - precursor of Dopamine and Carbidopa is a drug that helps it to be absorbed.

appetite, nausea, vomiting

• Dopamine Agonists – nausea, fatigue, sleepiness

• Amantidine – restlessness, dizziness, agitation, confusion, postural hypotension, urinary retention, peripheral oedema, toxic psychosis (mania)

Drugs for Parkinson’s

Disease

Antipsychotic drugs (neuroleptics)

Phenothiazines; with side chain:• Propylamine

– Chlorpromazine (Clonactil)• Very sedative• Moderate anticholinergic and

extrapyramidal effects

• Piperidine– Thioridazine

• Moderately sedative• Very anticholinergic and fewer

Others:• Butyrophenones

– Haloperidol (Haldol, Serenace)

• Atypical drugs– Clozapine (Clozaril)– Risperidone (Risperdal,

perdamel)– Sulpiride (Dolmatil)

• Very anticholinergic and fewer extrapyramidal effects

• Piperazine– Fluphenazine (Modicate)– Trifluoperazine (Stelazine)

• Less sedative• Less anticholinergic and more

pronounced extrapyramidaleffects

Neuroleptics (antipsychotics)Typical Neuroleptics –

• Phenothiazines – Chlorpromazine (Chloractil, Largactil), Flupentixol (Fluanxol), Fluphenazine, Methotrimeprazine, Pericyazine, Perphenazine, Pipotiazine, Prochlorperazine (Buccastem, Proziere, Stemetil), Thioridazine, Trifluoperazine; Benperidol, Haloperidol (Haldol, Serenace), Pimozide, (Ami)Sulpride(Dolmatil, Sulptil), Zuclopenthixol

Atypical Neuroleptics -

• Aripipazole (Abilify), Carbamazepine (Tegretol, Teril, Timonil), Clozapine (Clozaril), Olanzapine (Zyprexa), Quetiapine (Seroquel), Risperidone (Risperdal), Zotepine(Zoleptil)

Actions

• All these drugs block DA receptors (opposite of

Side Effects

• Parkinsonian Effects – loss of balance, tremors, tardive dyskinesias

• Blurred Vision

• Dry Mouth

• Sedation

• Confusion, Constipation

• Urinary Retention

• Drowsiness• All these drugs block DA receptors (opposite of

antiparkinsonian drugs). Atypical neuroleptics also block 5HT receptors

Uses

• Delusions, hallucinations, disorganised or catatonic speech or behaviour :

– Schizophrenia, Schizophreniform Disorder, Schizoaffective Disorder, Delusional Disorders, Psychotic Disorders e.g. Personality Disorders, Mania

– Aggressive behaviours of Autism

– Tourette’s syndrome (Pimozide)

– Anti-emetics

• Drowsiness

• Postural Hypotension

• Dizziness, Fainting

• Amenorrhea

• Infertility, Impotence

• Significant Weight Gain

• Neuroleptic syndrome – muscle rigidity, fever, stupor, unstable blood pressure

• Seizures

Antipsychotic drugs

(neuroleptics)

Anxiolytics and hypnotics

• Anxiolytics

– Benzodiazepines BDZ (central depressants)

• Diazepam (Valium) (seizures)

• Lorazepam (Ativan)(seizures)

• Alprazolam (Xanax)

– Antidepressants• Amitriptyline

• Hypnotics

– BDZ (central depressants)

• Temazepam (Tenox)

• Lormetazepam (Noctamid)

• Nitrazepam (Mogadon)

– Others• Amitriptyline

(depression/anxiety)

• Buspirone (anxiolytic)

• Citalopram (Cipramil)(panic disorders)

– β – Blockers• Propranolol

– Others• Zopiclone (Zimovane)

• Chloral hydrate

• Clomethiazole (Heminevrin)

• (Barbiturates) not used

much because of dependence

Anxiolytics Benzodiazepines (BDZ)

• Alprazolam (Xanax)

• Chlordiazepoxide (Librium)

• Clonazepam (Klonopin)

• Diazepam (Valium)

• Lorazepam (Ativan)

Action

• Acts on GABA : BDZ receptor Cl- channel complex; this increases the duration of chloride ion channel opening at the

Side effects

• Amnesia (anterograde and retrograde)

• Drowsiness

• Lack of coordination

• Libido/erection problems

• Disinhibition/euphoria

• Confusion

• Blurred vision

Herbal treatments

• Certain herbs are reputed to have anxiolyticproperties, including the following:

• Rhodiola rosea (Arctic Weed/Golden Root) chloride ion channel opening at the GABAA receptor, thus increases the efficacy of GABA . By increasing the available amount of GABA typically have relaxing, anti-anxiety and anti-convulsive effects

Uses

• Panic/anxiety disorders

• Insomnia

• Seizures

• ‘muscle relaxant’

• Rhodiola rosea (Arctic Weed/Golden Root)

• Bacopa monnieri (Brahmi)

• Hypericum perforatum (St. John's Wort)

• Matricaria recutita (German Chamomile)

• Mitragyna speciosa (Kratom)

• Piper methysticum (Kava)

• Sceletium tortuosum (Kanna)

• Scutellaria spp. (Skullcap)

• Valeriana officinalis (Valerian)

• Cannabis sativa (Marijuana)

Anxiolytics and

hypnotics

Antidepressants• Tricyclics

– Amitriptyline(Elavil, Tryptizol, Laroxyl)

– Clomipramine (Anafranil)

– Dosulepin (Prothiaden, Dolthep)

– Lofepramine (Gamanil)

• SSRI

– Citalopram (Cipramil)

– Fluoxetine (Prozac)

– Paroxetine (Seroxat)

Actions

Side effects

• dry mouth

• dry nose

• blurry vision

• lowered gastrointestinal motility or constipation

• urinary retention

• cognitive and/or memory Actions

• Block reuptake of Noradrenalin abdserotonin (5HT) and antagonise many other receptors (causing side effects)

Uses

• Depression

• Bipolar disorders

• Anxiety

• Social phobia

• cognitive and/or memory impairment

• Increased body temperature

• Drowsiness

• anxiety

• emotional blunting

• Confusion

Antidepressants

MAOI’s (monoamine oxidaseinhibitors)

• Isocarboxazid (Marplan)

• Moclobemide (Aurorix, Manerix)

• Phenelzine (Nardil)

• Selegiline (Eldepryl, Emsam)

• Tranylcypromine (Parnate)

Action

Side effects

• Sleep disturbances

• Nausea

• Dizziness

• Sometimes headaches

• Rarely confusion

• Blocks monoamine oxidase, which breaks down neurotransmitters (nor-adrenaline, dopamine, serotonin) after presynaptic uptake), thereby potentiating their effects

Uses

• Depression

Antidepressants

Lithium

• Camcolit, Priadel

Actions

• Largely unknown. Thought to work by decreasing release of NE and DA while stabilising or even increasing release of 5HT (in

Side Effects

• Nausea, Diarrhoea, Drowsiness, Frequent Urination (polyuria), Frequent Thirst (polydypsia), Weight Gain, Hand Tremors, Acne

Toxic effects

• Should have regular checks of kidney function, urine analysis, serum urea and creatinine,

increasing release of 5HT (in animal studies).

Uses

• Mania in bipolar disorders

• Prophylaxis of depression

• Cluster headaches

serum urea and creatinine, thyroid and heart function

• Vomiting, Diarrhoea, Ataxia, Tremors, Convulsions, Coma, Confusion, Hyper reflexes, Seizures, Nerve Damage, Hypotension, Albuminuria, Cardiac Arrhythmias

Epileptics/anticonvulsants• Acetazolamide, Carbamazepine (Tegretol, Teril,

Timonil), Clonazepam (Rivotril), Clobazam, Diazepam (Rimapam, Tensium, Valclair, Valium), Gabapentin (Neurontin), Levetiracetam, Lamotrignine (Lamictal), Lorazepam (Ativan), Phenobarbital (Gardenal), Phenytoin (Epanutin), Piracetam, Primidone (Mysoline), (Sodium) Valproate (Convulex – valproic acid, Epilim, Orlept), Tiagabine, Topiramate, Vigabatrin

Actions

• Anticonvulsants – bind with sodium or chlorine channels to slow action potentials.

• Some antipsychotics also bind with sodium

Side Effects

• Common are : Nausea and Vomiting, Headache, Confusion, Hallucinations,

• Also

• Sedation, Ataxia

• Penytoin – megaloblastic anemia, hyperglycemia

• Carbamazapine – stupor, comia, respiratory depression, blurred vision, rashes, liver toxicity, hyponatremia –• Some antipsychotics also bind with sodium

channels (Carbamazepine, Lamotrignine)

• Some anxiolytics (benzodiazepines –clonazepam, clorazepate, diazepam, lorazepam) and barbiturates (Phenobarbital) bind with chorine channels

• Some drugs increase GABA release – which then binds with chlorine channels (Gabapentin) or interfere with its breakdown (valproate)

Uses

• Sedative, anticonvulsant and muscle relaxant

rashes, liver toxicity, hyponatremia –needs frequent blood and liver function tests when on drug

• Phenobartital, Primidone – vertigo, psychosis, rashes, agitation, confusion

• Valproate – tremors, rashes, alopecia, thrombocytopenia, inhibition of platelets, liver failure

• Lamotrignine – rashes, internal bleeding

• Levetiracetam – insomnia

• Topiramate – somnolence, anxiety, weight loss

Epileptics

Opioid analgesics - narcotics Opioid analgesics

– Strong• Morphine• Diamorphine (Heroin)• Dihydrocodeine (DF118)

• Oxycodone (Oxycontin/OxyNorm)• Tramadol (Zydol)

– Moderate• Codeine

– Endogenous peptides• Endorphins • Enkephalins

• Actions• Acts on morphine receptors (μЌδσ)

Side effects

• Respiratory Depression – main cause of death in opioid overdose

• Constipation

• Sedation

• Menstrual Changes

• Nausea and Vomiting

• Addiction -• Acts on morphine receptors (μЌδσ)• Uses – pain:

– myocardial infarction – sickle cell crisis – pre- and postoperatively – trauma – severe chronic pain, e.g., cancer– pain from kidney stones – severe back pain

• Withdrawal symptoms – tearing, runny nose, sweating, yawning, flushing, palpitations, spasms and twitches, shaking fever, restlessness, irritability, insomnia

Opioid analgesics

Drugs used in nausea and vertigo (antiemetics)

• Dopamine antagonists

– Prochlorperazine (Stemetil)

– Metoclopramide (Maloxon,

Primperan, Migramax, Paramax)

– Betahistine (Serc), Domperidone(Motilium),

• 5HT3 (serotonin) antagonists

– Ondansetron (Zofran, Emital)

– Granisetron (Kytril)

• Antimuscarinic drugs

Side effects

• Nausea

• Indigestion

• Drowsiness

• Sedation

• Diarrhoea

• Headaches

• Breast Distension• Antimuscarinic drugs

– Hyoscine (Kwells)

• Antihistamines

– Cinnarizine (Stugeron)

– Promethazine (Phenergan)

– Cyclizine (Valoid)

Uses

• Nausea and Vomiting from:

• Vertigo/Dizziness (Betahistine)

• Gastroentiritis (Domperidone)

• Chemotherapy

• Breast Distension

• Muscle Spasms/Tremors

• Restlessness

• Reduced Libido

• Constipation

Drugs used in nausea and vertigo (antiemetics)

Non-steroidal anti-inflammatory drugs (NSAI’s)• Salicylic acid derivatives

– Aspirin • Propionic acid derivatives

– Ibuprofen (Brufen, Ibugel)– Fenbufen (Lederfen)– Naproxen (Naprosyn)

• Others– Diclofenac (Cataflam, Voltarol)– Indomethacin (Indocid)

– Nambumatone (Relifex)

– Phenylbutazone• Selective COX2 inhibitors

– Etoricoxib (Arcoxia)

– Celecoxib (Celebrex)

Side effects

• All NSAIDs (except for Aspirin) increase likelihood of cardiovascular events, including myocardial infarctions, CVA’s and worsening of hypertension.

• All increase GI irritation, ulceration, haemorrhage, and perforation; can also cause Kidney toxicity

• Aspirin (high/toxic doses) -– Celecoxib (Celebrex)

• Analgesic only– Paracetamol

Action

• Block prostaglandin synthesis, thus reducing inflammation

Uses

• Inflammation• Fever• pain

• Aspirin (high/toxic doses) -respiratory paralysis, coma, oedema, hyperkalaemia, anaphylactic shock in 15% of patients

• Mefenamic Acid and Meclofenamate– severe diarrhoea, bowel inflammation, haemolytic anaemia

• Acetaminophen – skin rash, allergic reactions, long term - renal tubular necrosis, hypoglycaemia, hepatic necrosis

Non-steroidal anti-inflammatory (NSAI’s)

Corticosteroids

• Hormones

– Hydrocortisone [Cortisol, Cortisone] (Hydrocortone)

• Synthetic

– Prednisolone/prednisone

– Methylprednisone (Depo –mendrone)

– Betamethasone (Betnesol,

Betnelan)

Side effects

• Stomach upset

• Increased appetite

• Diabetes mellitus

• Immunosuppression

• Osteoporosis

• Elevated liver enzymes

• Cushing’s disease

Long term effectsBetnelan)

– Dexamethasone

– Triamcinolone (Adcortil)

Action

• Prevents phospholipid release, reducing prostaglandin synthesis

Uses

• Inflammation

• Immunosuppressant

Long term effects

• hyperglycaemia, insulin resistance, diabetes mellitus, osteoporosis, anxiety, depression, gastritis, colitis, hypertension, erectile dysfunction, hypogonadism, hypothyroidism, amenorrhoea, retinopathy.

Corticosteroids

Hyperthyroidism/Thyrotoxicosis

• Methimazole, Carbimazole(Neo Mercazole),

Propylthiouracil

Actions

• Inhibit formation of T3 and T4

Side effects

• Headache, dizziness, nausea, rashes, itching, hair loss, mouth ulcers

• Reduced Immunity

• Feverand T4

Uses

• Hyperthyroid conditions:

• Palpitations, hypertension, insomnia, headaches, aversion to heat

• Fever

• Lymphadenopathy (swollen lymph nodes)

Hypothyroidism

• Levothyroxine (Eltroxin), Liothyronine

Actions

• Is a synthetic form of T4

Uses

• Underactive thyroid,

Side effects

• Anxiety

• Agitation

• Diarrhoea

• Weight Loss

• Sweating

• Flushing

• Muscle cramps• Underactive thyroid, manifesting as: weight gain, fatigue, aversion to cold, cold extremities, low metabolism

• Muscle cramps

• Angina

• Palpitations

• Overdose – hyperthyroid! -> in addition, insomnia, headaches, irritability, aversion to heat, hypertension

Thyroid and Anti-thyroid drugs

Posterior pituitary drugs

• Desmopressin (Desmotabs, Nocutil), Vasopressin (ADH), Bromocriptine (Parlodel)

Actions

• Desmopressin metabolitiesreplace Vasopressin and encourage water conservation and release of blood coagulation factors. Bromocriptine inhibits

Side effects

• Desmopressin – headache, nausea, vomiting, nosebleeds, stomach pain, convulsions, thrombosis, myocardial infarction

• Bromocriptine – confusion, factors. Bromocriptine inhibits secretion of prolactin from the pituitary gland.

Uses

• Diabetes Insipidus (Type 1) –polyuria, and nocturnal enuresis

• High Prolactin levels – infertility and impotence

• Bromocriptine – confusion, dizziness, nausea, vomiting, headache, constipation, dyskinesias

Sex hormones and drugsInfertility

• Anti-oestrogen

– Clomifene (Clomid)

Action

• Selective Estrogen Receptor Modulator (SERM), increasing production of gonadotropins by inhibiting negative feedback on the hypothalamus

• Gonadotrophins

– Choriogonadotropin alfa (Ovitrelle)

• Side effects

• Headache

• Oedema

• Hypertension

• Nausea and Vomiting

• Post menopausal Uterine Bleeding

Long term use– Follitropin alfa, Lutotropin Alfa

(Pergoveris)

Actions

• Causes ovulation

• Androgens

– Testosterone (Andropatch)• Actions

• Stimulates leydig cells to synthesize testosterone

Uses

• Infertility in men

Long term use

• Thromboembolisms

• Myocardial infarction,

• Breast/Uterine Cancer

• Raloxifene – hot flushes, leg cramps, swollen ankles, leg pain swelling and ulcers

Sex hormones and drugs

• Female sex hormones (HRT)

– Oestradiol (Climera, Evorel)

– Estradiol, Medroxyprogesterone(Indivina)

– Medroxyprogesterone (for endometriosis) (Provera)

– Levonogestrel (emergency contraception) (Levonelle)

Actions

Side effects

• Headache

• Upset stomach, stomach cramps or bloating

• Diarrhoea

• Appetite and weight changes

• Changes in sex drive or performance

• Nervousness

• Brown or black patches on the skin Actions

• Replaces hormones

Uses

• Osteoporosis

• Menopause symptoms

– hot flashes, vaginal dryness, urinary stress incontinence, chilly sensations, dizziness, fatigue, irritability, and sweating

• Brown or black patches on the skin

• Acne

• Swelling of hands, feet, or lower legs due to fluid retention

• Changes in menstrual flow

• Breast tenderness, enlargement, or discharge

• Sudden difficulty wearing contact lenses

Sex hormones and drugs

Antidiabetic drugs • Insulin preparations(Type 1 im)

• Short acting– Insulin, rDNA

Saccharomyces cerevisiae(Actrapid)

– Insulin aspart (Novomix)

• Intermediate acting– Huminil 1

• Type 2• Sulphonylureas

– Glibenclamide (Daonil)– Glicazide (Daimicron)– Glimepiride (Amaryl)– Glipizide (Glibenese)

• Glucosidase inhibitors– Acarbose (Glucobay)

– Huminil 1

– Insuman basal

• Long acting– Insulatard

– Levimir

– Lantus

– Acarbose (Glucobay)

• Biguanides– Metformin (Glucophage)

• PPAR gamma antagonists– Pioglitazone (Actos)– Rosiglitazone (Avandia)

Type 2 Antidiabetic drugs • Sulphonylureas

– Glibenclamide (Daonil)

– Glicazide (Daimicron)

– Glimepiride (Amaryl)

– Glipizide (Glibenese)

Actions

– Act on the pancreas and block ATP potassium channels which causes influx of calcium and insulin release. Also reduce glucagon levels and stimulate binding of insulin to target tissues.

Side effects

• Hypoglycaemia: fatigue, tremors, hunger, headache, palpitations, blurred vision, confusion, cold sweats, convulsions, coma

• Weight gaininsulin to target tissues.

• Glucosidase inhibitors

– Acarbose (Glucobay)

• Biguanides

– Metformin (Glucophage)

Actions

– Inhibits glucogenesis in the liver reducing the output of glucose from the Liver and blood sugar levels

• HyperInsulinemia

• Acarbose and Metformin –GI disturbances: flatulence, diarrhoea, cramping. Rarely lactic acidosis

Anti-diabetic drugs

Antibacterial –Nucleic acid inhibition• Sulphonamides (UTI)

– Nitrofurantoin (Furandantin, Macrobid)

– Trimethoprim (pneumocystis carinii) (Monotrim Suspension)

Actions

– Prevents DNA synthesis

– Inhibits B5 (important in AA synthesis)

Uses

• Respiratory Tract Infections

• GI Tract Infections

• Urinary Tract Infections

Side effects

• nephrotoxicity due to crystalluria,

• hypersensitivity reactions from rash to angioedema.

• Serious blood reactions e.g. granulocytopenia, thrombocytopenia, megaloblasticanemia, leukopenia, haemolytic anemia. • Genital Tract Infections

– Sulphonamides (UTI)

– Strep pneumoniae

– Nocardia asteroide,

– H influenzae,

– E Coli, Shigella

– Trimethoprim

– Listeria monocytogenes, H Influenzae, Legionella pneumonphillia, E Coli, Proteus mirabilis, Salmonella typhi, Shigella

anemia.

• Other side effects – nausea, vomiting, stomach pain.

• Contraindicated in pregnant

women and infants under 2

months

Antibacterial –Nucleic acid inhibition

• Quinolones

– Ciprofloxacin (Ciproxin,

Biofloxcin)

– Levofloxacin (Tanavic)

– Moxifloxacin (Avelox)

Actions

– Prevents DNA synthesis

– Inhibits B5 (important in AA synthesis)

Side effects

• Diarrhoea/nausea, vomiting,

• Headache/dizziness, phototoxicity.

• To be avoided in pregnancy and breast feeding and in synthesis)

Uses

– Neisseria gonorrhoeae, Bacillus anthracis, Enterobacteriaceae, E Coli, Psuedomonas, Klebsiellapneumoniae, Proteus mirabilis, Serratia marcescens, Shigella, H Influenzae, Legionella pneumophillia(Legionnaires Disease), Mycoplasma

pneumonia, Chlamydia pneumonia, Mycobacterium tuberculosis

and breast feeding and in children under 18.

• Can cause articular cartilage erosion, causing ruptured tendons in adulthood.

Antibacterial –Nucleic acid inhibition• 5-Nitroimidazoles

– Metronidazole (anaeobic infn.) (Flagyl, Metronide)

– Rifampicin (TB, Leprosy) (Rifadin)

Actions

– Prevents cell walls formation and inhibits protein folate and RNA synthesis.

Uses

– Mycobacterial infections:

– TB

Side effects

• Dapsone – methemoglobinemia, peripheral neuropathy, erythema nodosum

• Ethambutol – optic nerve neuritis, decrease in vision, colour blindness, worsens gout

• Isoniazid – hypersensitivity reactions, peripheral neuritis, paresthesias, convulsions in patients prone to seizures, mental abnormalities, optic nerve neuritis– TB

– Leprosy

– Pneumocystis

– Neisseria Meningitidis,

– H Influenzae

– Lung Infections

– Genitourinary Tract Infections

– Meningitis

mental abnormalities, optic nerve neuritis

• Rifampicin – nausea and vomiting, fever, rash, jaundice. Caution in patients with chronic liver disease, alcoholics and the elderly

• Rifabutin – rash, neutropenia, liver function text abnormalities, anemia, thrombocytopenia

• Pyrazinamide – gout, nausea, hepatitis, hyperuricemia, rash, joint pain

Antibacterial – nucleic acid inhibition

Antibacterial – cell wall inhibition

• Penicillins– Benzylpenicillin (Crystapen)– Penicillin V (Calvepen)

• Broad spectrum– Amoxicillin (RTI, GU, gynae,

gonorrhoea, peritonitis, bac endocardiitis,

septicaemia, wound infn)(Augmentin, Amoxil)

– Ampicillin (septicaemia, endocarditis, osteomyelitis, meningitis, abdominal

(Penbritin, Clonamp)

• Cephalosporins• Orally active

– Cefaclor (RTI, otitis media, soft tissue, UTI, nasopharyngeal) (Distaclor, Keftid)

– Cefuroxime (Zinacef)– Cephalexin (RTI, otitis media,

soft tissue, GU, dental infn) (Keflex)osteomyelitis, meningitis, abdominal

surgery)(Penbritin, Clonamp)

• Penicillinase resistant– Flucloxacillin (staph infn.,

endocarditis) (Flucillin)

• Antipseudomonal– Piperacillin, Tazobactam (RTI,

intra-abdominal, septicaemia,

neutropenia) (Tazocin)

(Keflex)

– Ceftriaxone (RTI, Renal, UTI, septicaemia, meningitis, soft tissue, gonorrhoea) (Rosephin)

• Vancomycin (staph enterocolitis)

(Vancocin Matrigel)

• Teicoplanin (staph inf prophylactic)

(Targocid)

Antibacterial – cell wall inhibition

Side Effects

• Diarrhoea

• Nausea and Vomiting

• Abdominal Pain

• Swollen Tongue

• Bruising

• Jaundice

• Rash• Rash

• Itching

• Fever

• Sore Throat

• Nephritis

• Neurotoxicity - especially in Epileptic patients

• Eosinophilia

Antibacterial – cell wall inhibition

Antibacterial – protein synthesis inhibition• Actions

• Attack bacterial ribosomes, prevents protein synthesis

• Tetracyclines– Doxycycline (RTI, sinusitis, UTI, STI, cholera, plague)

(Vibramycin)– Minocycline (acne) (Minosil)

– Uses– Bacillus antracis– Brucella– Vibrio cholerae– Yersinia pestis– Clostridium perfingens

• Aminoglycosides

• Chloramphenicol (eye infn) (Chloromycetin)• Macrolides

– Clarythromycin (RTI, acute otitis media, H.Pylori, ST infn) (Klacid)

– Erythromycin (Erythroped, Erythyrocin)

– Azithromycin (RTI, otitis media, genital chlamidia infn)

(Zithromax, Azromax)

– Uses– Staph aureus/pneumoniae/pyogenes– Corynebacterium diphtheriae– Bordetella pertussis– Capmyobacter jejuni– Treponema palladium

• Others• Aminoglycosides– Amikacin (pseudomonal infn) (Amikin)– Tobramysin (chronic airways infn pseudomonas)

(Cidomycin, Genticin)

– Gentamicin

• Uses– Enterococcus Gram +ve– Brucella– Klebsiella– Pseudomonas– Yersinia Pestis

• Others– Dalfopristin, Quinpristin (Serious gram+ infn)

(Synercid)

Antibacterial – protein synthesis inhibition

Antifungal drugsAntifungal• Polyenes

– Amphotericin B (Aspergilliosis, candida,

cryptococcal meningitis, histoplamosis) (Albecet)– Nystatin (Candida) (Mycostatin)

• Imidazoles[Topical]

– Clotrimazole (Candida) (Canestan)– Ketoconazole (candida) (Nizoral)

• Triazoles

– Fluconazole (candida, meningitis) (Diflucan, Byfluc, Diflazole)

– Itraconazole (Candida, histoplasmosis, cryptococcal infn) (Sporanox)

– Side effects

– Nausea, vomiting, skin irritation, H/A• Clotrimazole – skin burns• Fluconazole – abdominal distension,

diarrhoea, hepatitis• Flucytosine – neutropenia,

thrombocytopenia, bone marrow depression, alters liver function tests, severe enterocolitis

• Itraconazole – hypokalemia, hypertension, oedema

• Ketoconzole –abdominal pain, gynecomastia, decreased libido, impotence, menstrual problems, affects liver function tests, cryptococcal infn) (Sporanox)

• Flucytosine (Candida, crytococcal) (Ancotil)• Terbinafine (histoplasmosis, cryptococcal [not

meningitis], systemic fungal) (Lamasil, Fungafine)• Caspofungin (candida, aspergillus) (Cancidas)

problems, affects liver function tests, jaundice

• Miconazole – vaginal irritation• Amphotericin –fever, bleeding symptoms,

abdominal pain, muscle and joint pain• Nystatin – diarrhoea• Terbinafine – blurred vision, affects liver

function tests, neutropenia, hepatotoxicity

Antiviral drugs

• Penetration inhibitors

– Amantadine (flu prophylactic) (Symmetrel)

• Nucleoside Reverse Transcriptase Inhibitors (NTRI’s)

– Stavudine (HIV) (Zerit)

– Zidovudine (HIV) (Retrovir)

– Tenofovir (HIV) (Viread)

• Non-Nucleoside Reverse Transcriptase Inhibitors NNRI’s

– Nevirapine (HIV) (Viramune)

• Side effects

• Acyclovir – headache, diarrhoea, nausea and vomiting, renal dysfunction (high dose)

• Famiclovir – headaches, nausea, adenocarcinomas and testicular toxicity

• Ganciclovir/Valganciclovir – GI upset, neutropenia, carcinogenic, embryotoxic

• Indinavir – headache, GI upset, nephrolithiasis, hyperbilirubinemia

• Lamivudine – headache and dizziness– Nevirapine (HIV) (Viramune)

• Protease inhibitors

– Ritonavir (HIV) Kaletra)

– Saquinavir (HIV) (Invarase)

• Neuramanidase inhibitor

– Zanamivir (flu) (Relenza)

• Herpes Simplex

– Aciclovir (Zovirax)

– Famciclovir (recurrent genital herpes) (Famvir)

• Lamivudine – headache and dizziness

• Oseltamivir – GI upset

• Ribaviran – elevated bilirubin, transient anemia

• Rimantidine – GI upset

• Valacyclovir – GI upset, thrombocytopenia purpura

• Zanamivir – headache, sore throat, cough, wheezing

Antifungal and antiviral drugs

Drugs – parasites - helminths

• Intestinal nematodes• Roundworm

– Piperazine, levamisole, mebendazole,

• Hookworm– Bephenium, Trichlorethylene, Thiabendazole

• Whipworm – Mebendazole, thiabendazole

• Threadworm (common in children)– Thiabendazole,

– Medendazole (GIT worms) (Vermox)

• Tissue Nematodes

• Platyheminths• Trematodes

– Schistosomiasis• Praziquantel

– Cestodes• Praziquantel• Niclosamide

• Side effects• Albendazole – headache, nausea, liver toxicity,

agranulocytosis, pancytopenia• Dying parasites can cause inflammatory • Tissue Nematodes

– Filaria (blood worms, if in lymphatics

can cause obstruction and swelling)• Diethylcarbamazine

• Dying parasites can cause inflammatory responses, headache, vomiting, fever, convulsions and mental changes.

• Mebendazole – abdominal pain and diarrhoea• Ivermectin - fever, headache, dizziness,

somnolence and hypotension. • Praziquantel – drowsiness, dizziness, malaise, GI

disturbance and poor appetite• Thiabendazole – dizziness, poor appetite,

nausea, vomiting, erythema multiforme, Stevens-Johnson syndrome (fever, skin lesions, mucous membrane ulcers)

Drugs – parasites - helminths

Drugs parasites - protozoa

• Malaria (Plasmodium)– Tissue schizonticide

• Primaquine

– Blood schizonticide (If clinical attack)

• Proguanil (Paludrine)

• Mefloquine (Larium)

• Chloquine (Avloclor)

• Amoebic dysentery– Metronidazole (Flagyl)

• Giardiasis– Metronidazole (Flagyl)

• Trochonomiasis– Metronidazole (Flagyl)

• Pneumocytosis• Chloquine (Avloclor) • Pneumocytosis– Pentamidine (Pentacarinat)

• Leishmanisasis– Stibogluconate

(Pentostam)

• Tripanosomiasis– Suramin (Germanin)

Drugs parasites - protozoa• Amoebiasis (Amoebic Dysentery)

(Metronidazole, Paromomycin, Tinidazole)

• Cryptosporidiosis (Paromomycin)

• Malaria (Chloroquine, Doxycycline, Mefloquine, Quinine, Quinidine, Primaquine, Proguanil, Pyrimethamine)

• Giardiasis (Metronidazole, Tinidazole)

• Pneumocystis Pneumonia

• Chloroquine – nausea, diarrhoea, abdominal pain, headache, dizziness, hearing disorders, mood changes (see Mefloquine), rash, blurred vision

• Doxyclycline – nausea, vomiting, diarrhoea, mouth ulcers, headache, rash, photosensitivity, blurred vision

• Mefloquine – nausea, vomiting, headache, dizziness, abdominal pain, depression, anxiety, panic attacks, hallucinations, delusions, hearing disorders

• Pneumocystis Pneumonia (Atovaquone, Pentamidine, Sulfonamides)

• Toxoplasmosis (Atovaquone, Pyrimethamine, Sulfonamides)

• Trichomoniasis (Metronidazole, Tinidazole)

• Trypanosomiasis (Sleeping sickness) (Pentamidine, Primaquine)

delusions, hearing disorders

• Primaquine – abdominal bloating, diarrhoea, methemoglobinemia, granulocytopenia, agranulocytosis, hemolytic anemia

• Quinine – nausea, vomiting, diarrhoea, headache, tinnitus, dizziness, rash, hearing loss, blurred vision

• Malarial Drugs – discoloration of mucous membranes and nail beds, angina, palpitations, arrhythmias

Drugs parasites - protozoa

Drugs used in cancer

Inhibit DNA synthesis– Cytarabine (inhibits DNA

polymerase)

• Antimetabolites– Methotrexate

• lymphocytic leukaemia, choriocarcinoma, Burkitt'slymphoma, breast

– Capecitabine (Xeloda)• colorectalcancer and breast cancer

– Fluorouracil

– Raltitrexed

Side effects

• Nausea• Vomiting• heart arrhythmias• Neutropenia• Hair loss

– Raltitrexed

– Mercaptopurine– lymphocytic leukemia

• Vinca alkaloids -antimicrotubule– Vinblastine

– Hodgkin’s lymphoma, cancer of lung/breast/testicles, head and neck

– Vincristine– Non-Hodgkin’s lymphoma,

lymphoblastic leukaemia,

• Taxanes– Paclitaxel

Drugs used in cancerInactivate DNA

• Alkylating agents

– Chlorambucil (Endoxana)

– multiple myeloma and lymphocytic leukemia

– Ifosfamide (Mitozana)

– Estramustine - prostate cancer

– Cyclophosphamide (Endoxana)

– Burkitts lymphoma, breast

• Alkylating agents are carcinogenic and can cause treatment induced neoplasms many years after treatment

• Common:

• Vomiting

• Stomatitis– Burkitts lymphoma, breast

cancer

– Melphalan (Alkaran)

– multiple myeloma and lymphocytic leukaemia

– Bulsulfan (Busulfex, Myleran)

– Granulocytic leukaemia

• Stomatitis

• poor appetite, diarrhoea

• hair loss

• bone marrow suppression

Drugs used in cancer

• Antibiotics (cytotoxics)

– Doxorubicin

– Hodgkin’s lymphoma, lung, breast, bladder, stomach, thyroid and uterine cancer, Kaposi’s sarcoma

– Actinomycin D (inhibits

transcription)

– gestational trophoblastic neoplasia, Wilms' tumour and

Side effects

• Nausea

• Vomiting

• heart arrhythmias

• Neutropenia

• Hair lossneoplasia, Wilms' tumour and rhabdomyosarcoma

• Steroid hormones

– Glucocorticoids

– Oestrogens

– Anti-oestrogens

– Androgens

• Monoclonal antibodies

– Rituximab (B-Cell lymphoma) (Mabthera)

• Hair loss

Drugs used in cancer

Adverse drug reactions

• Type I – anaphylaxis– Penicillins

– Cephalosporins

– Sulphonamides

– Contrast media

• Type III – complex mediated– Penicillins

• Type II – cytotoxic– Haemolytic anaemia

• Sulphonamindes• Penicillin• Quinidine• Methydopa

– Agranulocytosis

Adverse drug reactions

Frequently from immune reactions – hypersensitivity

– Penicillins

– Sulphonamides

– Thiazides

• Type IV – cell mediated– Penicillins

– Cephalosporins

– Local anaesthetics

– Phenytoin

– Agranulocytosis• Carbimazole• Clozapine

– Thrombocytopenia• Quinidine• Heparin

– Teratogenesis• Alcohol (FAS)• Anticancer drugs• Warfarin

Immune disorders: hypersensitivity and autoimmune diseases

Type I /allergy/atopy(IgE)

ForeignAtopic dermatitis· Allergic urticaria· Hay fever· Allergic asthma· Anaphylaxis· Food allergy(Milk , Egg, Peanut, Tree nut, Seafood, Soy, Wheat), Penicillin allergy

Autoimmune none

Type II /ADCC(IgM , IgG)

ForeignAutoimmune

Pernicious anemia· Hemolytic disease of the newborn

CytotoxicAutoimmune hemolytic anemia· Idiopathic thrombocytopenic purpura· Bullous pemphigoid · Pemphigus vulgaris· Rheumatic fever· Goodpasture's syndrome

" Type 5"/ receptor

Graves' disease· Myasthenia gravis

Type III(Immune

Foreign Henoch-Schönlein purpura· Hypersensitivity vasculitis· Reactive arthritis· Rheumatoid arthritis·Farmer's lung· Post-streptococcal glomerulonephritis· Serum sickness· Arthus reaction(Immune

complexFarmer's lung· Post-streptococcal glomerulonephritis· Serum sickness· Arthus reaction

Autoimmune Systemic lupus erythematosus· Subacute bacterial endocarditis

Type IV/cell-mediated(T-cells)

Foreign Contact dermatitis· Mantoux test

Autoimmune Diabetes mellitus type 1· Hashimoto's thyroiditis· Guillain-Barré syndrome· Multiple sclerosis·Coeliac disease· Giant cell arteritis

GVHD Transfusion-associated graft versus host disease

Unknown/multiple

Foreign Hypersensitivity pneumonitis(Allergic bronchopulmonary aspergillosis) · Transplant rejection· Latex allergy(I+IV)

Autoimmune Sjögren's syndrome· Autoimmune hepatitis· Autoimmune polyendocrine syndrome(APS1, APS2) ·Autoimmune adrenalitis

Poisoning - Antidotes

• Carbon monoxide

– Hyperbaric O2

• Paracetamol

– Acetylcyteine

– Methionine

• Opioids

• Ethylene glycol

– Ethanol

– Fomepizole

• Organophosphorus insecticides

– Atropine/pralidoxime

• Lead/Mercury

– Chelating \agents

• Salicyclates/phenobarbital• Opioids

– Naloxone

• Iron

– Desferrioxamine

• Salicyclates/phenobarbital

– Alkaline diuresis (NaHCO3)

• Theophylline/barbiturates

– Charcoal haemoperfusion

Poisoning

HIV/AIDS Drugs• Nucleoside Inhibitors: Abacavir

(Ziagen), Lamivudine (Epivir), Lamivudine/ Zidovudine (Combivir), Lamivudine/Zidovudine/Abacavir(Trizivir), Didanosine (Videx), Stavudine (Zerit), Zalcitabine (Hivid), Zidovudine (AZT) (Retrovir)

• Nucleotide Inhibitors: Tenofovir(Viread)

• Non-Nucleoside Inhibitors: Efavirenz

• Abacavir – GI disturbance, headache, dizziness, fever, malaise, rash

• Didanosine/Stavudine – peripheral neuropathy (numbness and tingling)

• Zalcitabine – rash, stomatitis, peripheral neuropathy

• Zidovudine – headaches, bone marrow toxicity, severe anemia, leukopenia, seizures

• Tenofovir – nausea, vomiting, diarrhoea

• Efavirenz – dizziness, headache, vivid dreams, loss of concentration, rash

• Nevirapine – headache, fever, rash, elevated • Non-Nucleoside Inhibitors: Efavirenz(Sustiva), Nevirapine (Viramune)

• Protease Inhibitors: Amprenavir(Agenerase), Indinavir (Crixivan), Nelfinavir (Vircept), Ritonavir(Norvir), Lopinavir/Ritonavir (Kaletra), Saquinavir (Fortovase, Invirase)

Action

• RNA replication

• Nevirapine – headache, fever, rash, elevated liver function tests, epidermal necrolysis, Stevens-Johnson syndrome

• Protease Inhibitors (in general) – nausea, vomiting, diarrhoea, paraesthesias, headaches, diabetes, hypertriglyceridemia, hypercholesterolemia, fat redistribution

Gout• Allopurinol (Caplenal, Cosuric,

Rimapurinol, Xanthomax, Zyloric)

– interferes with uric acid formation

• Colchicine

– Probenecid inhibits reabsorption of uric acid in the kidneys – increasing uric acid excretion

Side effects

• Nausea and Vomiting

• Abdominal pain

• Diarrhoea

• Colchicine – long term

– Myopathyacid excretion

• Probenecid

– prevents granulocyte migration and inhibits leukotrienes (reduces inflammation

– Myopathy

– Agranulocytosis

– aplastic anaemia

– hair loss

Immunosuppression

• Azathioprine (Azasan, Imuran)

– prevents lymphocyte generation

• Cyclosporine (Neoral, Restasis)

– work by blocking IL2 synthesis and subsequent T cell proliferation.

• Mycrophenolate (Cellcept, Myfortic), Tacrolimus

Side effects

• All agents can make a patient prone to life threatening infections

• Azathioprine – nausea, vomiting, suppression of bone marrow

• Cyclosporine – kidney and liver toxicity, lymphomas, hypertension, hyperkalemia, Myfortic), Tacrolimus

– inhibits formation of RNA, DNA and protein synthesis, and also prevents B and T cell proliferation

Uses

• Autoimmune Disorders

• Organ or Tissue Transplants – kidney, liver and heart transplants (in combination with steroids)

hypertension, hyperkalemia, tremors, hirsuitism

• Mycophenolate – diarrhoea, lymphoma, leukopenia, sepsis

• Tacrolimus - kidney and liver toxicity, lymphomas, hypertension, hyperkalemia, tremors, seizures, hallucinations, diabetes mellitus

Erectile Dysfunction Drugs • Sildenafil (Viagra)

• Tadalafil (Cialis),

• Vardenafil (Levitra)

• Action

• phosphodiesterase inhibitors, which block a specific phosphodiesterase (PDE5) which breaks down the chemical that initiates and maintains erections.

• Side effects

• Headache

• Flushing

• Dizziness

• Indigestion

• Nasal Congestioninitiates and maintains erections.

• They also potentiate Nitric Oxide action and so are contraindicated with concurrent use of nitrate drugs for angina, and Alpha adrenergic antagonists

• Nasal Congestion

• Blurred Vision

• Altered Colour Blindness

• Persistent Erections

• Chest Pain