Drugs

2. INTRODUCTION
• Functions: Drugs can alter the function of the
central nervous system (CNS) to provide
• • 1. Anticonvulsant effects
• 2. Tranquilization (sedation)
• 3. Analgesia

3. Neurotransmitter-receptor
relationship
• Neurotransmitters released by a presynaptic neuron combine with receptors on the plasma
membrane of a postsynaptic neuron, altering its membrane potential.
• 1. Neurotransmitters in the CNS include
• dopamine,
• y-aminobutyric acid (GABA),
• acetylcholine (ACH),
• norepinephrine,
• serotonin,
• histamine,
• glutamate,
• glycine,
• substance P, and many neuropeptides.

4. • 2. Receptors for neurotransmitters are the site of action for exogenous
drugs.
• a. The neurotransmitter-receptor complex may directly alter the
permeability of the cell membrane by opening or closing specific ion
channels.
• b. Second messengers. The neurotransmitter-receptor complex may
initiate a sequence of chemical reactions that alter ion transport across
the membrane, thereby altering the membrane potential. Specific
intracellular signal molecules, or second messengers, may be generated.
The second messenger system sustains and amplifies the cellular
response to drug-
• receptor binding. The vast majority of these neurotransmitters
• have G protein-coupled receptors (GPCRs).

5. Blood-brain barrier (BBB)
• Circulating drugs must cross BBB in order to gain access to
the neurons of the brain
• 1. Drugs that are cross BBB most readily
• a. lipid soluble, b. small in molecular size,
• c. poorly bound to protein,
• d. nonionized at the pH of cerebrospinal fluid (CSF)
• 2. The BBB tends to increase in permeability in the presence
of inflammation or at the site of tumors.
• 3. The BBB is poorly developed in neonates; hence,
chemicals can easily gain access to the neonatal brain.

6. ANTICONVULSANT DRUGS
• Only a few of the anticonvulsant drugs available for
human use have been proven to be clinically useful
in dogs and cats.
• a. Some of the drugs are too rapidly metabolized in
dogs to be effective, even at high dosages.
• b. Clinical experience un known in cats. Cats are
generally assumed to metabolize drugs
• more slowly and poorly than dogs.

7. Mechanism of action
• Anticonvulsant drugs stabilize neuronal membranes
• a. They may act directly on ion channels, resulting
in hyperpolarization of the neuronal membrane.
• b. They activate GABA-gated Cl- channels increasing
the frequency of Cl- channel opening produced by
GABA, thereby evoking hyperpolarization of the
neurons.

8. • Therapeutic uses
• Anticonvulsant drugs reduce the
• 1. Incidence,
• 2. Severity,
• 3. Duration of seizures
• Adverse effects:
• 1. seizures, or status epilepticus may follow rapid
cessation of administration of these drugs
• 2. Enzyme induction
• 3. Hepatotoxicity

9. Barbiturates
• Phenobarbital
• Chemistry. Phenobarbital is an oxybarbiturate.
• Mechanism of action. Barbiturates activate GABA-gated Cl-
channels, thereby evoking hyperpolarization of the neurons.
• Pharmacologic effects
• (1) Phenobarbital limits the spread of action potentials and
thus elevates the seizure threshold.
• (2) Most barbiturates have anticonvulsant effects, but
phenobarbital is unique in that it usually produces this effect
at lower doses than those necessary to cause pronounced CNS
depression (sedation).

10. • Therapeutic uses. Phenobarbital is used for the long-term control
of seizures.
• Phenobarbital is usually administered orally
• It is not useful for terminating an ongoing seizure because the
time span from administration until the onset of effect is too long
(~20 minutes).
• When given orally, its GI absorption is practically complete in all
animals. Peak levels occur in 4-8 hours after oral dosing in dogs.
• Adverse effects: Sedation, polydipsia, polyuria, and polyphagia
are common side effects.
• Dogs develop a tolerance to the sedative effects after 1-2 weeks.

11. Primidone
• Primidone is a deoxybarbiturate (an analog of
phenobarbital).
• Primidone is slowly absorbed after oral
administration in dogs
• In cats, the metabolism to phenobarbital is slower
• Adverse effects. Prolonged use of primidone in dogs
may lead to decreased serum albumin and elevated
serum concentrations of liver enzymes. Occasionally,
serious liver damage occurs.

12. Pentobarbital
• Pentobarbital is an oxybarbiturate
• Therapeutic uses. Pentobarbital will terminate seizures
at a dose that produces anesthesia. This dose usually
results in significant cardiopulmonary depression but
may be the only way to control status epilepticus
• It has a rapid onset (<1 minute) after IV injection and
short duration of action.
• Adverse effects
• Pentobarbital is a CNS depressant irritating when
administered perivascularly.

13. Phenytoin
• Phenytoin is a hydantoin derivative
• Mechanism of action: Phenytoin stabilizes neuronal
membranes and limits the development and spread of
seizure activity.
• a. It reduces Na+ influx during the action potential reduces
Ca2+ influx during depolarization, and promotesNa* efflux,
inhibition of the spread of seizure activity.
• b. K+ movement out of the cell during the action potential
may be delayed, producing an increased refractory period
and a decrease in repetitive depolarization.

14. • Therapeutic uses
• a. Phenytoin is an anticonvulsant drug; however,
because of its short t 1/2 in dogs, use of phenytoin
may be impractical.
• b. Because of its lidocaine-like effects, phenytoin
has been recommended for the treatment of
digitalis-induced ventricular arrhythmias in dogs

15. Benzodiazepines
• Diazepam, midazepam, clonazepam, and lorazepam are used
as anticonvulsants.
• drugs for the treatment of status epilepticus (continuous
seizure activity lasting >5 minutes or recurrent seizures
between
• . They can be used as a maintenance anticonvulsant in cats. a
very limited use as a maintenance anticonvulsant in
dogs,because the development of tolerance occurs rapidly in
this species due to drug metabolism into inactive metabolites.
because the development of tolerance occurs rapidly in this
species due to drug metabolism into inactive metabolites.

16. • Diazepam
• Mechanism of action.
• Benzodiazepines activate GABA-gated Cl channels to
potentiate the channel opening activity of GABA, thereby
evoking hyperpolarization of the neurons.
• Therapeutics uses
• In cats, it is administered orally for seizure control developing
tolerance make diazepam
• In dogs, it is administered IV for the control of status
epilepticus and cluster seizures. ⚫ in dogs as a maintenance
anticonvulsant because it has a short t 1/2 of 2-4 hours

17. • Adverse effects
• (1) Changes in behavior (irritability, depression, and
aberrant demeanor) may occur after receiving
diazepam.
• (2) Cats may develop acute fatal hepatic necrosis

18. Midazolam
• Therapeutic uses. Midazolam is used as an
anticonvulsant for status epilepticus, muscle relaxant,
tranquilizer, and appetite stimulant the same way as
diazepam
• Pharmacokinetics. Midazolam has a shorter elimination
t 1/2 of 77 minutes in dogs, which is shorter than
diazepam (~3 hours). Readily crosses BBB
• Adverse effects. Midazolam may cause mild respiratory
depression, vomiting, restless behavior, agitation, and
local irritation.

19. • Clonazepam
• Therapeutic uses. The uses are the same as diazepam
without distinct advantages over diazepam.
Clonazepam alone has very limited value as a
maintenance anticonvulsant because of the rapid
development of drug tolerance.
• Adverse effects. Tolerance to the anticonvulsant
effects in dogs, Gl disturbances, including vomiting,
hyper-salivation, and diarrhea/ constipation may
occur.

20. • Lorazepam
• Mechanism of action
• a. It is hypothesized that Brenters neurons via Cl-channels,
resulting in hyperpolarization of the neuronal membrane.
• b. Barbiturates and benzodiazepines, which enhance Cl
conductance, may act in synergy with KBr to hyperpolarize
neurons, thus raising the seizure threshold.
• Therapeutic uses
• a. KBr is administered orally to treat refractory seizures in dogs.
The use in cats is not recommended, since it evokes severe
asthma in this species.
• b. It is used in combination with phenobarbital to terminate
refractory generalized tonic-clonic convulsions in dogs.

21. • Adverse effects
• a. Transient sedation at the beginning of therapy may
• Occur.
• b. Gl effects. Stomach irritation can produce nausea and
vomiting. Vomiting, anorexia, and constipation are
indications of toxicity.
• c. Polydipsia, polyuria, polyphagia, lethargy, irritability,
and aimless walking are additional adverse effects of Br-.
d. Pancreatitis may be precipitated by Br-.
• e. Severe asthma can be seen in Br--treated cats.

22. • Valproic acid and sodium valproate
• Valproic acid is a derivative of carboxylic acid. It is
structurally unrelated to other anticonvulsant drugs.
• Therapeutic uses
• a. In dogs, valproic acid is effective in controlling
seizures when given orally, but its short t 1/2 makes it
impractical for long-term use. It is a second to fourth-
line anticonvulsant that may be useful as an adjunctive
treatment in some dogs.
• b. Its clinical usefulness in cats has not been evaluated.

23. • Adverse effects
• a. Gl disturbances and hepatotoxicity. Vomiting,
anorexia, and diarrhea, which may be diminished by
administration with food. Hepatotoxicity, including liver
failure, is a potential adverse effect in dogs.
• b. CNS effects (sedation, ataxia, behavioral changes,
etc.), c. Dermatologic effects (alopecia, rash, etc.),
hematologic effects (thrombocytopenia, reduced
platelet aggregation, leukopenia, anemia, etc.),
pancreatitis, and edema.

24. • Gabapentin. It is a synthetic GABA analog that can cross BBB to
exert its anticonvulsant effect.
• Mechanism of action. GABA content in neurons is increased by
gabapentin. However, the main effect of gabapentin is due to its
inhibition of voltage dependent Ca2+ channels to decrease
neuronal Ca2+ levels, thereby inhibiting excitatory
neurotransmitter release (e.g., glutamate).
• Therapeutic uses. Gabapentin may be useful as adjunctive
therapy for refractory or complex partial seizures, or in the
treatment of chronic pain in dogs or cats. It is administered orally.
• Adverse effects. Sedation, ataxia, and mild polyphagia are
noticeable side effects. Abrupt discontinuation of gabapentin may
cause seizures.

25. • Levetiracetam. It is used orally as an adjunctive therapy for
refractory canine epilepsy. It is well tolerated in dogs and an
initial prospective trial in cats was favorable
• Mechanism of action. Levetiracetam inhibits
hypersynchronization of epileptiform burst firing and
propagation of seizure activity.
• It binds synaptic vesicle protein 2A in the neuron; the
interaction with this neuronal vesicular protein may account
for levetiracetam's anticonvulsant effect.
• Adverse effects. It has little side effects, which include changes
in behavior, drowsiness, and GI disturbances (vomiting and
anorexia). Withdrawal of this drug should be slow in order to
prevent "withdrawal" seizures.

26. • Felbamate is a dicarbamate drug and is used orally in dogs to treat refractory epilepsy as an
adjunctive therapy or a sole anticonvulsant agent for patients with focal and generalized
seizures.
• At clinical doses, felbamate does not induce sedation and thus is particularly useful in the
control of obtunded mental status due to brain tumor or cerebral infarct.
• Mechanism of action
• a. Blockade of NMDA receptor-mediated neuronal excitation.
• b. Potentiation of GABA-mediated neuronal inhibition.
• c. Inhibition of voltage-dependent Na* and Ca2+ channels.
• Adverse effects.
• a. liver dysfunction. it should not be given to dogs with a liver disease hepatotoxicity,
• b. Reversible bone marrow depression is rarely seen in dogs. These dogs may have
thrombocytopenia and leucopenia.
• c. Keratoconjunctivitis sicca and generalized tremor are rarely seen side effects of felbamate in
dogs.

27. • Zonisamide is a sulfonamide-based anticonvulsant drug or an
adjunctive therapy to control refractory epilepsy in dogs with
minimal adverse effects. It is administered orally twice a day.
• the cost could be a problem for using this drug in dogs. The
drug has not been studied sufficiently in cats to be
recommended for this species.
• Mechanism of action. Zonisamide inhibits voltage- dependent
Na+ and Ca2+ channels of neurons to induce hyperpolarization
and decreased Ca2+ influx
• Adverse effects. Zonisamide has high safety margin in dogs.
The reported side effects include sedation, ataxia, and
anorexia.

28. • CNS STIMULANTS (ANALEPTICS)
• Doxapram is used most frequently in veterinary medicine as a CNS stimulant.
• 1. Mechanism of action. Doxapram stimulates respiration, which is a result of
direct stimulation of the medullary respiratory centers and probably via
activation of carotid and aortic chemoreceptors.
• 2. Therapeutic uses
• a. Doxapram is used to arouse animals from inhalant and parenteral anesthesia
or anesthetic overdose. The depth of anesthesia is reduced, but the effect could
be transient. b. Doxapram is not effective in reviving a severely depressed
neonate and is not a good substitute for endotracheal intubation and
ventilation.
• 3. Adverse effects.
• High doses of doxapram may induce seizures. Hypertension, arrhythmias,
seizures, and hyperventilation leading to respiratory alkalosis can happen.

29. TRANQUILIZERS, ATARACTICS,
NEUROLEPTICS, AND SEDATIVES
• These terms are used interchangeably in veterinary
medicine to refer the drugs that calm the animal and
promote sleep but do not necessarily induce sleep,
even at high doses. Ataractic means "undisturbed";
neuroleptic means "to take hold of nerves."
tranquilized animals are usually calm and easy to
handle, but they may be aroused by and respond to
stimuli in a normal fashion (e.g., biting, scratching,
kicking). When used as pre-anesthetic medications,
these drugs enable the
• use of less general anesthetic.

30. • Phenothiazine derivatives include acepromazine,
promethazine, chlorpromazine, fluphenazine,
prochlorperazine, and trimeprazine.
• Mechanism of action. Phenothiazine derivatives
affect the CNS at the basal ganglia, hypothalamus,
limbic system, brain stem, and reticular activating
system. They block dopamine, a1-adrenergic and
serotonergic receptors.

31. • Pharmacologic effects
• CNS effects
• (1) The tranquilizing effects( depression of the brain stem via blockade of dopamine and 5-HT
receptors.
• (2) All phenothiazines decrease spontaneous motor activity.
• Cardiovascular effects
• 1. Hypotension (al-adrenergic receptor blockade and a decrease in the sympathetic tone)
• 2. Reflex sinus
• 3. Antiarrhythmic effects
• 4. Inotropic effect.
• Respiratory effects :Respiratory depression
• GI effects 1. Motility is inhibited 2. Emesis is suppressed
• Effects on blood. Packed cell volume decreases
• Metabolic effects
• 1. Hypothermia/hyperthermia
• 2. Hyperglycemia Hyperprolactinemia.

32. • Therapeutic uses a. tranquilization.
• b. antiemetics.
• c. prior to use of inhalant anesthetics can reduce
the incidence of arrhythmias sensitization to
catecholamines.
• d. Promethazine and trimeprazine are used to
control allergy, because they block H1-receptors.

33. • Adverse effects. There is no reversal agent for this class of drugs. a. Accidental intracarotid
administration in horses results in the immediate onset of seizure activity and, sometimes,
death.
• b. They inhibit cholinesterase (ChE) and may worsen the clinical signs of anti-ChE
poisoning. They should not be given to animals within 1 month of treatment with an
organophosphate compound.
• c. The H1-antagonistic effect makes phenothiazines an undesirable drug for sedation of
animals prior to allergy testing.
• d. Paraphimosis may occur in stallions, which is due to relaxation of retractive penis
muscles via al-receptor blockade. Thus, phenothiazines should be used cautiously or
avoided altogether in breeding stallions.
• Contraindications
• a. Anti-ChE poisoning or suspected treatment with anti-ChE antiparasitic drugs.
• b. History of blood loss and hypotension.
• c. Avoid in animals with moderate to severe liver dysfunction or portacaval shunt.

34. • a2-Adrenergic agonists These drugs activate a2-
adrenergic receptors in the CNS, thereby causing
analgesia, sedation, and skeletal muscle relaxation.
• Mechanism of action. a2-Agonists activate a2-
receptors that are Gi/o-coupled receptors; Gi/o
mediates many inhibitory effects on the nervous
systems and endocrine glands
• High doses of xylazine, detomidine, and romifidine
also activate a1-receptors.

35. • Pharmacological effects
• Analgesia.
• (1) a2-Receptors are located on the dorsal horn neurons
of the spinal cord, they can inhibit the release of
nociceptive neurotransmitters, substance P and calcitonin
gene-related peptide (CGRP).
• (2) a2-Adrenergic mechanisms do not work through
opioidergic mechanisms, because cross- tolerance is not
usually present. a2-Agonist- mediated analgesia is not
reversed by opioid antagonists.

36. • Sedation.
• 1. Ruminants are most sensitive to a2-agonists, followed by cats, dogs, and are least sensitive to a2-agonists in
domestic animals.
• horses. Pigs
• 2. High doses of a2-agonists may induce CNS excitation, which is attributable to activation of al-receptors
• Skeletal muscle relaxation a2-Agonists produce skeletal muscle relaxation by inhibiting intraneuronal
transmission of impulses in the CNS.
• Emesis. It is induced in carnivores and omnivores, and is commonly seen in the cat,and less frequently in the
dog.
• Cardiovascular effects
• 1. Bradycardia,
• 2. hypertension is due to activation of the postsynaptic a2-receptors of vascular smooth muscle.
• 3. hypotension is caused by reduced norepinephrine release by the sympathetic nerve at the vascular smooth
muscle
• 4. Bradycardia (with or without sinus arrhythmia) is due to decreased norepinephrine release to the
myocardium, particularly the SA node. An increase in baroreceptor reflex during hypertension
• Renal effects. a2-Agonists induce diuresis through inhibiting vasopressin release
• Respiratory effects. a2-Agonists cause hypoxemia

37. • Neuroendocrine effects. a2-Agonists inhibit sympathoadrenal
outflow and decrease the release of norepinephrine and
epinephrine.
• (1) a2-Agonists inhibit insulin release; this effect is very
pronounced in ruminants, which results in a moderate to
severe hyperglycemia lasting up to 24 hours.
• (2) a2-Agonists increase growth hormone release by inhibiting
somatostatin release from the hypothalamus and stimulating
growth hormone-stimulating hormone release from the
median eminence. The a2-agonist-induced growth hormone
release is not sustained; consecutive daily drug administration
can only maintain increased secretion for <1 week.

38. • Therapeutic uses
• a2-Agonists are used as a sedative, analgesic, and
immobilizing agent.
• They are also used to induce epidural analgesia, - as
a preanesthetic, and as a part of the anesthetic
combination.
• xylazine-ketamine is a commonly used, but not very
safe, parenteral anesthetic combination

39. • Xylazine. It is approved by the FDA for use in the cat, dog, horses, and wildlife,
for example, deer and elk. However, it is also frequently used in other species,
particularly the cattle. It is administered IM, IV, or SC
• Adverse effects
• (1) Because of the Gl stasis associated with xylazine administration, bloat may
be a result.
• (2) Xylazine-induced bradycardia with sinus arrhythmia/arrest can be severe.
Close monitoring is needed; in very severe cases, the use of an a2-antagonist
may be necessary to save the animal.
• (3) Xylazine affects the thermoregulation center in the hypothalamus, thus it
produces hypothermia when the ambient temperature is low, and hyperthermia
when the ambient temperature is high. Thus, the use of xylazine to immobilize
wildlife should be performed with caution and the use of a2-antagonist to
control the pharmacological effects of xylazine (or other a2- agonists) in wildlife
is a must.

40. • Contraindications
• (1) Cardiac aberrations (2) Hypotension or shock
• (3) Renal insufficiency
• (4) Hepatic impairment
• (5) Epilepsy (because xylazine may precipitate seizures in susceptible animals).
• (6) Use of xylazine in combination with ketamine should be used only in young healthy animals
because this combination synergistically suppresses cardiopulmonary function of the animal.
• (7) Immediate collapse, convulsions, and sudden death can occur in horses given xylazine into
the carotid artery.
• (8) A cautious approach should be taken whenever xylazine is used in treatment of colic,
because xylazine's powerful analgesic effect can mask the underlying problem and because
xylazine can paralyze the GI tract.
• (9) Xylazine should not be given to animals (particularly mares and ruminants) within the last
month of pregnancy, since it may induce abortion. (
• 10) Xylazine should not be given to dehydrated animals or those with urinary obstruction
because of its potent diuretic effect.

41. • Detomidine (Dormosedan R ). It is approved by the FDA for use in horses. It is administered IM
or IV.
• a. Pharmacokinetics
• (1) The elimination t 1/2 is 1.2 hours for the IV dose and 1.8 hours for the IM dose.
• (2) Metabolism to detomidine carboxylic acid and hydroxydetomidine glucuronide and
thereafter excretion into the urine seems to be the major elimination route.
• b. Adverse effects
• (1) Following the recommended dose, piloerection, sweating, partial penis prolapse, and
salivation, and occasionally, slight muscle tremors may be seen.
• (2) Excessive doses of detomidine can induce CNS excitation. The above two side effects of
detomidine are also seen with the administration of other a2-agonists.
• (3) IV sulfonamides should not be used in detomidine-treated horses as potentially fatal
dysrhythmias may occur.
• (4) Detomidine at 400 µg/kg (10x of recommended dose of 40 µg/kg) daily for three
consecutive days can produce myocardial necrosis in horses.
• (5) Other adverse effects seen with xylazine administration may also occur in animals treated
with detomidine.

42. • Medetomidine (Dormitor R ). It is the most potent and
selective a2-agonist available for use in veterinary medicine. It
can induce light anesthesia in some individual animals; short
examinations/procedures can be performed in these animals
• Adverse effects. These are the same as stated in the xylazine
section and are the extension of the pharmacological effects of
the a2-agonist.
• However, since medetomidine is a very potent a2-agonist, the
adverse effects can be very severe. Thus, the use of an a2-
antagonist, for example, atipamezole may be needed to
reverse these adverse effects of medetomidine.

43. • Romifidine (Sedivet R ). It is for IV use in horses.
• Adverse effects. The adverse effects of romifidine
are similar to those of xylazine and detomidine.

44. SEDATIVES & HYPNOTICS
• Sedatives are drugs that calm the patient and
reduce anxiety without inducing normal sleep.
• Hypnotics are drugs that produce drowsiness and
encourage the onset of sleep

45. CLASSIFICATION OF DRUGS
• Barbiturates.
• Benzodiazepines (BDZ).
• Miscellaneous agents.
• Buspirone
• Chloral hydrate
• Zolpidem
• Zaleplon.

47. Drugs used in Urinary
System.

48. Pharmacology of commonly
used:
• Diuretics.
• • Antidiuretics.
• • Urinary Antiseptics.
• • Cholinergics & Anticholinergics.
• • Acidifiers & Alkalanizers.

49. • Pharmacology of commonly used:
• • Diuretics.
• • Antidiuretics.
• • Urinary Antiseptics.
• • Cholinergics &
• Anticholinergics.
• Acidifiers & Alkalanizers.

50. • Diuretics ("water pills") are the drugs which increase the urine
out put (or) urine volume. What is natreuretic agent? Any drug
when introduce into the body increases the out put of sodium ie.,
loss of sodium in urine.
• Diuretics are very effective in the treatment of conditions like:
• Chronic heart failure
• Nephrotic syndrome
• Chronic hepatic diseases
• Hypertension
• Pregnancy associated edema
• Cirrhosis of the liver.

51. NORMAL PHYSIOLOGY OF URINE
FORMATION
• Two important functions of the kidney are:-
• 1. To maintain a homeostatis balance of electrolytes
and water.
• 2. To excrete water soluble end products of
metabolites.
• Each kidney contains approximately one million
nephrons and is capable of forming urine
independently.
• The nephrons are composed of glomerulus, proximal
tubule, loop of henle, distal tubule.

52. • Approximately 1200 ml of blood per minute flows through
both
• kidneys.
• Ions such as sodium, chloride,calcium are reabsorbed.
• *Total amount of glucose, amino acids, vitamins, proteins
are
• reabsorbed. If the urine contains above it represents the
disorders.
• *For example proteins such as albumin in higher amounts
causes
• albuminaria.

53. GFR FORMATION
• ✓1 cardiac output -5 lit/min.
• Out of that 20% goes to kidneys i.e.1 lit/min.
• 1 lit of blood of has 40% of cells and 60% of plasma.
• ✓600 ml of plasma is not entered into glomerulus only a
part of plasma can enter into it and the rest pass through
the efferent arteriole.
• ✔Only 20% can enter into glomerelus that is 120 ml.
• ✔This 120 ml/min (180L/day) makes glomerular filtrate
(99%reabsorbed).
• ✔Urine output is about 1-1.5L/Day

54. Classification of Diuretics
• According to types:
• 1. High ceiling (Loop Diuretics)
• Furosemide
• Torsemide.
• 2. Thiazide Diuretics.
• Chlorothiazide.
• Hydrochloride thiazide.
• Benzthiazide.
• 3. Osmotic Diuretics: Mannitol.
• 4. Carbonic Anhydrase inhibitors: Acetazolamide.
• 5. Potassium sparing Diuretics.
• Spironolactone.
• Amiloride.

55. • Accordingto efficacy
• High efficacy diuretics: Loop diuretics
• Medium efficacy diuretics: Thiazide diuretics
• Weak diuretics:
• Carbonic Anhydrase inhibitors
• Osmotic diuretics
• Potassium sparing diuretics

56. Diuretics
• Mechanism of action
• Loop diuretics: They show their action by reducing absorption of
sodium at the level of the loop of henle. E.g Furosemide, Torsemide.
• Potassium sparing diuretics: Drugs which antagonized the effect of
aldosterone. E.g Spironolactone
• Thiazide: They inhibit the reabsorption of sodium and chloride ions
from distal convolutedtubules e.g Chlorothiazide.
• Osmotic: It inhibits reabsorption of water and sodium e.g mannitol.
• Carbonic anhydrase inhibitor: They suppress the activities of
carbonic anhydrase e.g acetazolamide.
•

57. • Indication and Uses
• Loop diuretics: Edema, Acute pulmonary edema(Acute LVF, M.I), cerebral
edema, hypertension, hypercalcemia and renal calcium stone.
• Thiazide: mild to moderate edema(Cardiac failure, nephrotic syndrome),
HTN, Diabetes insipidus, hypercalciuria/calcium stone, premenstrual tenses.
• Osmotic: Acute renal failure during prolonged surgery or trauma to prevent
or treat increase ICP, glaucoma.
• Carbonic anhydrase inhibitors: Glaucoma, epilepsy, acute motion sickness,
periodic paralysis.
• Potassium sparing: hyperaldosteronism, HTN, CHF, edema, combined with
furosemide, Thiazide to reduce potassium loss produced by these agents.

58. Drug examples and doses
S/ No Drugs Doses
1 Furosemide 20-80mg
2 Torsemide 5-10mg orally or IV OD
3 Chlorothiazide 500-1000mg PO or IV
OD or bid
4 Hydrochlorothiazide 25-50mg OD
5 Benzthiazide 25mg
6 Mannitol 50-100gm IV
7 Acetazolamide 125-250mg orally IV
8 Spironolactone 25-200mg/day in 1or 2
divided doses
9 Amiloride 5-10mg OD

59. Contraindications and precautions
• Osmotic: intracranial bleeding, CHF, pulmonary
congestion, edema, urinary tract obstruction.
• Loop: Hyponatremia, Severe sodium and water
depletion, Hypokalaemia, Renal failure, Addison's
disease.
• Potassium:Anuria, Hyperkalaemia, Acute or progressive
renal insufficiency.
• Thiazide: severe renal impairment, severe hepatic
impairment,hypersensitivity, pregnancy & lactation.
• Carbonic Anhydrase: Pregnancy & lactation, hepatic
insufficiency, severe pulmonary congestion.

60. Adverse effect
• Thiazide: Hypokalaemia, metabolic alkalosis, hyponatremia,
Dehydration, Hypotension, Hypercholesterolemia, Hyperuricemia,
Azotemia (in renal disease patient)
• Loop: Hypokalaemia, metabolic alkalosis, Hyperuricemia,
Hypomagnesemia, Dehydration (Hypovolemia), Hypotension,
Ototoxicity (Dose related hearing loss)
• Osmotic: Electrolyte imbalance, increase circulatory load and may
cause congestive heart failure.
• Potassium: Hyperkalaemia, metabolic acidosis, Gynecomastia,
(aldosterone antagonist), Gastric problems including peptic ulcer.
• Carbonic Anhydrase: Hypokalaemia, metabolic acidosis, skin rash.

61. • Drug interactions:
• 1. Simultaneously use of spironolactone and digoxin increases the risks
of digoxin toxicity.
• 2. Spironolactone effects may decrease with salicylates use.
• 3. Salicylates may cause carbonic anhydrase inhibitor toxicity.
• 4. These drugs may cause lithium toxicity by decreasing excretion of
lithium.
• 5. Use of digoxin may cause additive hypokalaemia, these increasing the
risk of digoxin toxicity and arrthymias.
• 6. Anticoagulants effect may increases with the use of these drugs
simultaneously.
• 7. Risk of ototoxicity may occurs when use with aminoglycosides.

62. Antidiuretics
• Introduction: An antidiuretics are the agent that
reduce urine volume, opposing diuresis.
• Mechanism of Action: Reduces urine flow by acting
reabsorption of water by kidney tubules
• • Indication & Uses:
• 1. Cranial Diabetes insipidus.
• 2. Primary nocturnal enuresis (bed wetting) 3.
Nocturia associated with multiple sclerosis.

63. Drug Examples & Doses
S/No Drugs Doses
1 Antidiuretic Hormone
(Vasopressin)
5-10units IU/SC
2 Desmopressin 100-400mcg orally
1-4mcg IV

64. • Contraindication & Precautions: Hypersensitivity,
impaired renal function, with ongoing diuretic
treatment, Caution in CV disease, edema,
hypertension, cystic fibrosis, fluid and electrolyte
imbalance, pregnancy and lactation.
• •Adverse effect: Nasal irritation, Rhinitis, Abdominal
cramps, Urge defecate, fluid retention, congestion,
Ulceration, nausea, pallor, Backache in females (due
to uterine contraction)

65. Urinary Antiseptics
• Introduction: Drugs used for urinary tract infects which kill or
inhibit the growth of microorganism.
• Mechanism of Action: There are bacteriostatic drug. They inhibit
the growth of different species of bacteria in urine.
• Indication & Uses:
• 1. Sulphonamide are used to treat infection causes by susceptible
organism in urinary tract.
• 2. Methenamine is used to prevent recurrent urinary tract
infection
• Adverse effects: Fever, Rash, Crystalluria, Nausea,
Vomiting,Photosensitivity reaction, Stevens Johnson's syndrome

66. Drug examples & Doses
S/No Drugs Doses
Sulphonamides
1 Co-trimoxaxole 80mg+400mg
2 Sulfadiazine 500-1000mg
3 Sulfamethoxazole 1-2gm orally every 6hrly.
Miscellaneous
1 Flouroquinolones Ciprofoxacin-250-500mg,
Levofloxacin 250-500mg
2 Methenamine Igm orally
3 Nalidic acid Nalidixic Acid 500mg

67. • Contraindication & Precautions:
• 1gm orally younger than age 2yr.
• 2. History of Stevens Johnson syndrome.
• 3. Hypersensitive patients with sulphonamides.
• 4. Cautiously use in patient with mild to moderate renal or hepatic.
• Drug interaction:
• Sulphonamides may increase the effect of oral hypoglycemics.
• It may decrease the effectiveness of hormonal contraceptives.
• Increase risk of bleeding in patient who are taking anticoagulants.

68. Acidifiers & Alkalanizers
• Acidifiers :Sodium citrate, potassium citrate,
tartaric acid
• Alkalanizers: Sodium bicarbonate, acetazolamide

69. Acidic Alkaline pH immaterial
Nitrofurantoin Cotrimoxazole Chloramphenicol
Methanamine Aminoglycosides Ampicillin
Tetracyclines Cephalosporins
Cloxacillin Fluoroquinolones

70. References
• 1. Dr. P.K. Panwar, Essentials of pharmacology for nurses, AITBS pub.
2017, India, Pg no. 63-70.
• 2. Dr. Suresh k sharma, Textbook of pharmacology, pathology &
genetics for nurses, Jaypee pub. 2016 India Pg no 206-226. 3. Tara v.
Shanbhag, Smita shenoy, Pharmacology preparation manual for
undergraduate, Elsevier pub. 2014. Pg no. 150-160.
• 4. Marilyn Herbert - Ashton, Nancy Clarkson, Pharmacology, Jones
pub 2010 India, Pg no 486. & Barlet
• 5. Govind s. mittal, Pharmacology at a glance, Paras medical book
pub. 2009 India Pg no.20.
• 6. Madhuri Inamdar, Pharmacology in nursing. Vora medical pub.
2006 India 1st edition, Pg no 111-119.