Complete a medications form with each medication including their generic /brand name , category class, expected Pharmacological Action, Complications, Contraindications/Precautions, Interactions, Medication Administration, Evaluation of Medication Effectiveness, Therapeutic Use, Nursing Interventions, and Client Education.
Propofol Currently, propofol has super-
seded thiopentone as an i.v. anaesthetic, both for
induction as well as maintenance. It is an oily
liquid employed as a 1% emulsion. Unconscious-
ness after propofol injection occurs in 15–45
sec and lasts 5–10 min. Propofol distributes
rapidly (distribution t½ 2–4 min). Elimination
t½ (100 min) is much shorter than that of
thiopentone due to rapid metabolism.
Intermittent injection or continuous infusion
of propofol is frequently used for total i.v.
anaesthesia when supplemented by fentanyl.
It lacks airway irritancy and is not likely to
induce bronchospasm: preferred in asthmatics.
It is particularly suited for outpatient surgery,
because residual impairment is less marked and
shorter-lasting. Incidence of postoperative nausea
and vomiting is low; patient acceptability is very
good. Excitatory effects and involuntary
movements are noted in few patients. Induction
apnoea lasting ~1 min is common. Fall in BP
due primarily to vasodilatation with less marked
cardiac depression occurs consistently, and is
occasionally severe, but short lasting. Baroreflex
is suppressed; heart rate remains unchanged or
may decrease. Maintenance anaesthesia withpropofol produces dose-dependent respiratory
depression which is more marked than with
thiopentone. Effect of cerebral blood flow and
O2 consumption is similar to thiopentone. Pain
during injection is frequent; can be minimized
by combining with lidocaine.
Dose: 2 mg/kg bolus i.v. for induction; 100–200 μg/kg/min for maintenance
It is the most popular
oral anticoagulant. The commercial preparation
of warfarin is a mixture of R (dextrorotatory)
and S (levorotatory) enantiomers. The S form is
more potent and is metabolized relatively faster
by ring oxidation carried out by CYP2C9, while
R form is less potent and degraded by side chain
reduction carried out by CYP1A and CYP3A4.Both are partially conjugated with glucuronic acid
and undergo some enterohepatic circulation;
finally excreted in urine.
Warfarin is rapidly and completely absorbed
from intestines and is 99% plasma protein bound.
It crosses placenta and is secreted in milk;
however, quantity of active form is generally
insufficient to affect the suckling infant.
Adverse effects Bleeding as a result of exten-
sion of the desired pharmacological action is the
most important problem causing ecchymosis,
epistaxis, hematuria, bleeding in the g.i.t.
Intracranial or other internal haemorrhages may
even be fatal. Bleeding is more likely if therapy
is not properly monitored, or when INR exceeds
4, or interacting drugs/contraindications are present.
Treatment: of bleeding due to oral anticoagulants
• Withhold the anticoagulant.
• Give fresh blood transfusion; this supplies
clotting factors and replenishes lost blood.
Alternatively fresh frozen plasma may be used
as a source of clotting factors.
• Give vit K1 which is the specific antidote (see
p. 615), but it takes 6–24 hours for the clotting
factors to be resynthesized and released in
blood after vit K administration.
Adverse effects unrelated to anticoagulation are
given in Table 44.1. Cutaneous necrosis is a rare
complication that can occur with any oral
Phenindione produces serious toxicity; should not
Warfarin and acenocoumarol are considered to
be the most suitable and better tolerated drugs.
Dose regulation The dose of oral anticoagu-
lant must be individualised by repeated measure-
ment of prothrombin time; the aim is to achieve
a therapeutic effect without unduly increasing the
chances of bleeding.
The optimum ratio of PT during treatment with the oral
anticoagulant to the normal value (of the testing laboratory)
has been defined for various indications. But this value differs
depending on whether rabbit brain or human brain
thromboplastin (Tp) has been used for the test. A standardized
system called the International Normalized Ratio (INR) based
on the use of human brain Tp has been developed by WHO
and adopted in all countries.
Recommended INR for various indications of
1. Prophylaxis of deep vein thrombosis
and similar indications 2–2.5
2. Treatment of deep vein thrombosis,
pulmonary embolism, TIAs, hip surgery 2–3
3. Recurrent thromboembolism, arterial
disease (MI), prosthetic heart valves 3–3.5
Factors enhancing effect of oral anticoagu-
• Debility, malnutrition, malabsorption and
prolonged antibiotic therapy: the supply of vit
K to liver is reduced in these conditions.
• Liver disease, chronic alcoholism: synthesis
of clotting factors may be deficient.
• Hyperthyroidism: the clotting factors are
• Newborns: have low levels of vit K and clotting
factors (there should be no need of these drugs
in neonates anyway).
Factors decreasing effect of oral anticoagu-
• Pregnancy: plasma level of clotting factors is
• Nephrotic syndrome: drug bound to plasma
protein is lost in urine.
Genetic warfarin resistance: the affinity of
warfarin (as well as of vit K epoxide) to bind
to the reductase (VKOR) enzyme, which gene-
rates the active vit K hydroquinone, is low.
Dose of oral anticoagulant is 4–5 times higher.
Contraindications All contraindications to
heparin (see p. 619) apply to these drugs as well.
Factors which enhance the effect of oral
anticoagulants (see above) should also be taken
Oral anticoagulants should not be used
during pregnancy. Warfarin given in early preg-
nancy increases birth defects, especially skeletal
abnormalities. It can produce foetal warfarin
syndrome—hypoplasia of nose, eye socket, hand
bones, and growth retardation. Given later in
pregnancy, it can cause CNS defects, foetal
haemorrhage, foetal death and accentuates
Drug interactions A large number of drugs
interact with oral anticoagulants at pharmaco-
kinetic or pharmacodynamic level, and either
enhance or decrease their effect. These interactions
are clinically important (may be fatal if bleeding
occurs) and may involve more than one
mechanism; the exact mechanism of an interaction
is not always definable.
A. Enhanced anticoagulant action
1. Broad-spectrum antibiotics: inhibit gut flora
and reduce vit K production.
2. Newer cephalosporins (ceftriaxone, cefopera-
zone) cause hypoprothrombinaemia by the
same mechanism as warfarin —additive action.
3. Aspirin: inhibits platelet aggregation and
causes g.i. bleeding—this may be hazardous
in anticoagulated patients. High doses of
salicylates have synergistic hypoprothrom-
binemic action and also displace warfarin from
protein binding site.
4. Long acting sulfonamides, indomethacin,
phenytoin and probenecid: displace warfarin
from plasma protein binding.
5. Chloramphenicol, erythromycin, celecoxib,
cimetidine, allopurinol, amiodarone and
metronidazole: inhibit warfarin metabolism.
6. Tolbutamide and phenytoin: inhibit warfarin
metabolism and vice versa.
7. Liquid paraffin (habitual use): reduces vit K
B. Reduced anticoagulant action
1. Barbiturates (but not benzodiazepines),
carbamazepine, rifampin and griseofulvin
induce the metabolism of oral anticoagulants.
The dose of anticoagulant determined during
therapy with these drugs would be higher: if
the same is continued after withdrawing the
inducer—marked hypoprothrombinemia can
occur—fatal bleeding is on record.
2. Oral contraceptives: increase blood levels of
Digoxin is a cumulative drug. When
maintenance doses are given from the beginning,
steady state levels and full therapeutic effect are
attained after 4 × t½, i.e. 6–7 days.
Digoxin is the only cardiac glycoside available
widely and used clinically now.
Digoxin: DIGOXIN 0.25 mg tab., 0.05 mg/ml pediatric
elixir, 0.5 mg/2 ml inj. LANOXIN 0.25 mg tab,
CARDIOXIN, DIXIN 0.25 mg tab, 0.5 mg/2 ml inj.
Toxicity of digitalis is high, margin of safety is
low (therapeutic index 1.5–3). Higher cardiac
mortality has been reported among patients with
steady-state plasma digoxin levels > 1.1 ng/ml
but still within the therapeutic range during
maintenance therapy. About 25% patients deve-
lop one or other toxic symptom. The manifes-
Extracardiac Anorexia, nausea, vomiting and
abdominal pain are usually reported first: are due
to gastric irritation, mesenteric vasoconstriction
and CTZ stimulation. Fatigue, malaise, headache,
mental confusion, restlessness, hyperapnoea,
disorientation, psychosis and visual disturbances
are the other complaints. Skin rashes and
gynaecomastia are rare.
Cardiac Almost every type of arrhythmia can
be produced by digitalis: pulsus bigeminus, nodal
and ventricular extrasystoles, ventricular
tachycardia and terminally ventricular fibrillation.
Partial to complete A-V block may be the sole
cardiac toxicity, or it may accompany other
arrhythmias. Severe bradycardia, atrial extra-
systoles, AF or AFl have also been noted. In about
2/3 patients showing toxicity, extracardiac
symptoms precede cardiac; in the rest serious
cardiac arrhythmias are the first manifestation.
Treatment Further doses of digoxins must be
stopped at the earliest sign of toxicity; nothing
more needs to be done in many patients, especially
if the manifestations are only extracardiac.
(a) For tachyarrhythmias When caused by
chronic use of digitalis and diuretics (both induce
K+ depletion)—infuse KCl 20 m.mol/hour (max.
100 m. mol) i.v. or give orally in milder cases.
High extracellular K+ decreases binding of the
glycosides to Na+K+ATPase by favouring a
conformation of the enzyme that has lower affinity
for the glycoside, and K+ tends to antagonize
digitalis induced enhanced automaticity. When
toxicity is due to acute ingestion of large doses
of digoxin, plasma K+ may be high; it should
not be given from outside. In any case, it is
desirable to measure serum K+ to guide KCl
therapy. K+ is contraindicated if higher degree
of A-V block is present, because complete
A-V block and ventricular asystole may be
(b) For ventricular arrhythmias Lidocaine i.v.
repeated as required is the drug of choice. It
suppresses the excessive automaticity, but does
not accentuate A-V block. Quinidine, procaina-
mide and propafenone are contraindicated.
(c) For supraventricular arrhythmias
Propranolol may be given i.v. or orally depending
on the urgency.
(d) For A-V block and bradycardia Atropine
0.6–1.2 mg i.m. may help; otherwise cardiac
pacing is recommended.
Cardioversion by DC shock is contraindicated because
severe conduction defects may be unmasked in the digitalis
intoxicated heart. Attempts to enhance the elimination of
digoxin by diuretics or haemodialysis are not very effective.
PRECAUTIONS AND CONTRAINDICATIONS
(a) Hypokalemia: enhances digitalis toxicity.
(b) Elderly, renal or severe hepatic disease: patients are
more susceptible to digoxin toxicity.
(c) Myocardial ischaemia: severe arrhythmias are more
(d) Thyrotoxicosis: patients are more prone to develop
(e) Myxoedema: these patients eliminate digoxin more
slowly; cumulative toxicity can occur.
(f) Ventricular tachycardia: digitalis is contraindicated
because it may precipitate ventricular fibrillation.
(g) Partial A-V block: may be converted to complete
A-V block by digoxin.
(h) Acute myocarditis: Diphtheria, acute rheumatic carditis,
toxic carditis—inotropic response to digitalis is poor, more
prone to arrhythmias.
(i) Wolff-Parkinson-White syndrome: Digitalis is con-
traindicated because it decreases the ERP of bypass tract
in 1/3 patients. In them rapid atrial impulses may be trans-
mitted to ventricles → VF may occur. Digitalis can increase
the chances of reentry by slowing conduction in the normal
A-V bundle and accelerating it in the aberrant pathway.
1. Diuretics: cause hypokalemia which increases the risk
of digitalis arrhythmias; potassium supplements should be
2. Calcium: synergises with digitalis → precipitates toxicity.
3. Quinidine: reduces binding of digoxin to tissue proteins
as well as its renal and biliary clearance by inhibiting efflux
transporter P-glycoprotein → plasma concentration of digoxin
is doubled → toxicity can occur. Verapamil, diltiazem,
captopril, propafenone and amiodarone also increase plasma
concentration of digoxin to variable extents.
4. Adrenergic drugs: can induce arrhythmias in digitalized
patients; both increase ectopic automaticity.
5. Digoxin absorption may be reduced by metoclopramide,
sucralfate, antacids, neomycin, sulfasalazine. Absorption of
digoxin is increased by atropinic drugs, including tricyclic
6. Propranolol, verapamil, diltiazem and disopyramide:
may additively depress A-V conduction and oppose positive
7. Succinylcholine: can induce arrhythmias in digitalized
Uses-The two main indications of digitalis are CHF
and control of ventricular rate in atrial fibrilla-
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