IATROGENIC DISEASES

“First do no harm”-Hippocrates
 Introduction
• Iatrogenic disorders are diseases or symptoms induced in a
patient by physician's activity, manner, or therapy.

• These disorders occur when the deleterious effects of the

therapeutic or diagnostic regimen causes pathology
independent of the condition for which the regimen is given
 Causes of iatrogenic disorders
• Iatrogenic diseases can be brought about by:
• Diagnostic procedures (mechanical and radiological),

• Therapeutic regimens (drugs, surgery, other invasive

procedures),

• Hospitalization

• Treating doctor
 I. Adverse effects of diagnostic procedures
Procedure Adverse effects

Mechanical • Diagnostic aspiration of fluids may lead to hemorrhage, secondary infection, etc.
procedures
• Rapid pleural or peritoneal fluid aspiration and needle biopsies may lead to shock and
even death.

• Endoscopic procedure may cause perforation of hollow viscus.

Diagnostic radiology • Reactions to contrast media injected intravenously or intra-arterially may be mild,
moderate or severe, and some are potentially fatal.

• Intravascular contrast media may have a nephrotoxic reaction.

• Cerebral angiography may cause transient or permanent neurological deficits.

II. Adverse effects of drugs
 i. Drug induced cutaneous manifestations
Disorder Description/causative agent(s)
Alopecia Loss of hair -commonly caused by cancer therapy (radiotherapy, immunotherapy and
chemotherapy). Commonly implicated cytotoxic agents include bleomycin, etoposide,
cyclophosphamide, methotrexate among others
Photosensitivity This is cutaneous disease as a result of the combined effects of a chemical and light. Exposure
to either the chemical or the light alone is not sufficient to induce the disease; however, when
photoactivation of the chemical occurs, one or more cutaneous manifestations may arise.
Drugs: tetracyclines, NSAIDs, fluoroquinolones, sulphonamides, diuretics

Toxic epidermal necrolysis These are immune complex mediated hypersensitivity reactions characterized by blistering
(TEN) and Stevens- and peeling of the skin and the mucous membranes. They are serious systemic disorders with
Johnson syndrome (SJS) potential for severe morbidity and even death.
Drugs: tetracyclines, Barbiturates,Sulphonamides
Fixed drug eruptions These are well defined, round or oval patches of redness and swelling of the skin that
characteristically recur in the same site or sites each time a particular drug is taken;
Tetracyclines, sulphonamides, NSAIDs
Stevens-Johnson syndrome/TENS
Fixed drug eruptions
 ii. Drug-induced haematological disorders
Disorder Description/causative agent(s)
Megaloblastic • Phenytoin, phenobarbitone and primidone cause MA due to folic acid deficiency,
anaemia (MA) • colchicine, neomycin, paramino salicylic acid (PAS) due to vitamin B12 deficiency
• 6-mercaptopurine, 5 flurouracil,hydroxy-urea, acyclovir and zidovudine by interfering with DNA
metabolism

Hemolytic anemia • Immune Hemolytic Anemia (IHA) is characterized by destruction of red cells by antibodies acting
against antigens on the erythrocyte membrane.May be caused by e.g. aminopyrine, chlorpromazine
andtetracycline
• In G-6 PD deficient patients hemolysis may be caused by antimalarials (primaquine) and antibiotics
(nitrofurantoin). Hemolysis may also be precipitated by infection and fava beans.

Aplastic anaemia Aplastic anemia (AA) is characterized by pancytopenia with a hypocellular bone marrow. Drugs
implicated in inducing AA include antirheumatic drugs, antithyroid medications, antituberculous drugs,
NSAIDs, and anticonvulsants. Specific drugs cited include chloramphenicol, butazone, sulfonamide, gold
salts, penicillamine, amidopyrine, trimethoprim/sulfamethoxazole, methimazole, and felbamate

Neutropenia NSAIDs e.g. indomethacin, anticonvulsants e.g. phenytoin and carbamazepine, antithyroid drugs such as
thiouracil and methimazole
 Drug-induced haematological disorders
Disorder Description/causative agent(s)
Methemoglobinemia Characterized by excess production of methemoglobin, causing impairment in the
transport of oxygen. Drugs that induce methemoglobinemia either directly oxidize
hemoglobin or are metabolically activated to an oxidizing species. Examples:
dapsone,primaquine, benzocaine
Pure red cell aplasia This is characterized by normocytic anemia, reticulocytopenia, and absence of mature
(PRCA) marrow erythroid progenitors. PRCA is distinguished from aplastic anemia by
relatively normal leukocyte and platelet counts. PRCA has been reported to develop
after prolonged exposure to recombinant human erythropoietin. Other drugs causing
PRCA:immunosuppressants (azathioprine, FK506, antithymocyte globulin),
antibacterials (linezolide, isoniazid, rifampin, chloramphenicol), antivirals (interferon-
alpha, lamivudine, zidovudine), fludarabine, anticonvulsants (diphenyldrantoin,
carbamazepine, valporic acid), as well as chloroquine, allopurinol, ribavirin, and gold
 Drug-induced haematological disorders
Description/causative agent(s)

Immune This is characterized by platelet destruction- occurs when antibodies bind to

thrombocytopenia platelets leading to their clearance by the reticuloendothelial system (RES).
purpura (ITP) Classical causes of drug-induced thrombocytopenia are the quinine and
quinine-like drugs. The thrombocytopenia is typically sudden, severe, and may
be accompanied by bleeding.
Hypercoagulability This is associated with a propensity to development of both arterial and
venous thrombosis. Selective COX-2 inhibitors have been associated with
increased thrombotic cardiovascular events in several trials. These results led
to a voluntary withdrawal of rofecoxib from the worldwide market. Hormonal
therapies including oral contraceptives, hormone replacement therapy, and
tamoxifen (a selective estrogen receptor modulator with some agonist activity)
have all been associated with increased thrombotic risk.
 iii. Drug-induced GIT disorders
Disorder Description/causative agent(s)
Peptic ulcer Acetylsalicylic acid, NSAIDs,corticosteroids etc.
disease (PUD)

Pancreatitis Azathioprine, antiretroviral drugs.

Malabsorption Broad-spectrum antibiotics, cholestyramine and neomycin.

Hepatic damage Drug induced liver injury is a potential complication of nearly every
medication because liver metabolizes virtually all drugs.
Acute liver failure: (acetaminophen, halothane), chronic liver failure
(methyldopa), hepatocellular injury, veno occlusive disease
(cyclophosphamide) and hepatocellular carcinoma (sex and anabolic
hormones) can all occur. Drugs like halothane, acetaminophen and
phenytoin account for 20-50% of cases.
 iv. Drug-induced respiratory disorders
Disorder Example of causative agent

Airway obstruction Beta-Blockers and NSAIDs

Cough ACE inhibitors

Pulmonary Oral contraceptives

thromboembolism
 v. Drug –induced cardiovascular disorders
Disorder Example of causative agent

Exacerbation of Alpha blockers

angina

Arrhythmias Digitals, beta-adrenergic agents, tricyclic anti-

depressants and quinine,
Cardiomyopathy Daunorubicin

Hypertension Glucocorticoids and sympathomimetics

 vi. Drug-induced renal disorders
Mechanism of toxicity Causative drugs

Direct toxicity to the tubular cells Paracetamol, amphotericin B, cisplatin, sulphonamides

etc.
Function as an antigen and the Penicillins , cephalosporins, NSAIDs, anticoagulants,
resulting antigen antibody captopril etc.
reaction damages renal
interstitium and leads to acute
interstitial nephritis

Renal failure by reducing renal Noradrenaline and dopamine in high doses. NSAIDs
blood flow indirectly affect renal blood flow by inhibiting
production of prostaglandins.
 vii. Drug-induced neurological disorders
Disorder Causative agent

Peripheral Isoniazid, metronidazole,

neuropathy

Convulsions Amphetamine, Lithium, Phenothiazines

 viii. Drug-induced psychiatric disorders
Disorder Description Causative agents
Delirium A toxic confusional reaction characterized by Anticholinergics,
fluctuating clouding of consciousness, restlessness, glucocorticoids,
emotional changes (usually fear and perplexity, and phenothiazines
paranoid delusions and/ or visual hallucinations in
severe cases.)
Depression A serious mood disorder that causes severe symptoms Beta blockers,
that affect how the patient feels, thinks and handles glucocorticoids, oral
daily activities such as sleeping, eating, or working. It contraceptives
is characterized by feelings of hopelessness,
worthlessness, loss of interest in hobbies/pleasurable
activities, suicidal thoughts and attempts among
others
 ix. Drug-induced psychiatric disorders
Disorder Description Causative drugs
Drowsiness A feeling of sleepiness and low energy. Antihistamines, opioids,
benzodiazepines, tricyclic
antidepressants
Hallucinations Theses are false or distorted sensory experiences that can Beta blockers, methyldopa, narcotics
appear in the form of visions, voices or sounds, smells, or
tastes.

Mania This is a mental illness marked by periods of euphoria(intense All classes of antidepressants
excitement and happiness), delusions (false beliefs) and (SSRIs>atypicals> tricyclic
overactivity. antidepressants), glucocorticoids,
sympathomimetics
Paranoid states This is characterized by unfounded fear that something bad is Amphetamines
going to happen, and that other people are responsible for this
(mistrust and suscipicion of others). The patient experiences
intense anxious or fearful feelings and thoughts often related to
persecution, threat, or conspiracy.
 x. Drug-induced musculoskeletal disorders
Disorder Causative agents

Arthralgia Fluorides, growth hormone, Penicillin, Quinolones (in

children), Sulphonamides

Hyperuricemia and Cytotoxic drugs, Cyclosporine, Salicylates, Ethambutol,

gout Diuretics.

Mylagia/Myositis Clofibrate, , Gemfibrozil, Lovastatin,

Osteoporosis Anticonvulsants, Corticosteroids, Heparin, .

 Physician as the cause of disease
• The harm that a physician can do may be due to:
• Imprudent use of medicine or procedure.
• Unjustified remarks and misinterpretation of investigational data.

• The physician should be aware of the properties of drugs that

he prescribes and their potential dangers.
• Ignorance of the possibility of a reaction is a clear evidence of
negligence.

• The physician should warn the patient of the likely side effects.
 Hazards of hospitalization
• Ward patients may get hospital-acquired infections.
• Urinary tract infections and respiratory infections are the
commonest.

• There is also increased chance of infections associated with

diagnostic and therapeutic procedures and with antibiotic
resistant bacterial flora