Fluoxetine

Leila Jelle
HSM201-0027/2019
• Brand name – Prozac
• Drug class – Selective serotonin reuptake inhibitor
• Formulations – It is only available in an oral formulation available in oral
solution (20 mg/5 ml), tablet (10 mg, 20 mg, 60 mg), capsule (10 mg, 20
mg, 40 mg), and delayed-release capsule (90 mg)
• Pharmokinetics – Fluoxetine is metabolised to an active compound,
norfluoxetine, which has increased plasma concentrations and it’s half life
is about three times longer than fluoxetine. For this reason fluoxetine has
to be discontinued at least 4 weeks or longer before a monoamine oxidase
inhibitor is introduced so as to reduce the risk of serotonin syndrome.
• It is a potent inhibitor of the CYP2D6 isoenzyme. In the event that you
give the drug together with a substrate for the isoenzyme (such as a
TCA) it may lead to elevated levels of the drug and toxicity.
• Pharmacodynamics –Fluoxetine exerts its effects by blocking the
reuptake of serotonin into presynaptic serotonin neurons by blocking
the reuptake transporter protein located in the presynaptic terminal.
Fluoxetine also has mild activity at the 5HT2A and 5HT2C receptors. It
has minimal activity on noradrenergic reuptake.
• Bioavailability – 70%
• Dosage – 20 mg to 60 mg
• Uses – Major depression, generalised anxiety disorder, PTSD, OCD, panic
disorder, PMDD and bulimia
• Contraindications- Patients with known hypersensitivity, concomitant use
in patients receiving MAOI therapy, patients with hepatic disease,
pregnancy (increased risk of congenital heart defects).
• Drug price – About a 100 shillings per tablet
• Fun facts – Was introduced in 1988 and quickly became one of the most
commonly prescribed medications.
• Adverse effects – headaches, diarrhoea, nausea, vomiting, agitation
and anxiety. The late side effects include sexual dysfunction with
reduced libido, SIADH, serotonin syndrome.
MIDAZOLAM
Introduction

• A water soluble benzodiazepine

• Rapid onset of effects and short duration of action
• Available by oral, rectal, intranasal, intramuscular and intravenous

Pharmacodynamics
Acts as a short acting CNS depressant
Pharmacodynamic properties include: sedative, anxiolytic, amnestic,
muscle relaxant as well as hypnotic activities.
Enhances the inhibitory action of the amino acid NT GABA(inhibitory
NT) thus producing ;sedating effect relaxes skeletal muscles
Inducing sleep, anesthesia and amnesia
• Onset of sedation after IM injection in adults is 15 mins.
• Maximum sedation is 30-60 mins after injection
• Sedation post intravenous injection is 3-5 mins

Pharmacokinetics
Undergoes rapid absorption from GIT tract and prompt passage across
the blood brain barrier
Undergoes first pass effect thus only about 50% of administered dose
reaches the systemic circulation
Extensively bound to plasma proteins
Elimination half time is 1-4 hrs
Short duration of action is due to its lipid solubility thus rapid
redistribution from brain to inactive tissues and the rapid clearance.
• Can cross the human placenta and enter into fetal circulation
• Metabolized in the liver by Cytochrome P450-34A
• Clearance is reduced in association with old age, congestive heart failure ,
liver disease or condition that diminish CO and hepatic blood flow

• Therapeutic uses
Epilepsy
Sedation/anxiolysis/amnesia prior to or during diagnostic, therapeutic or
endoscopic procedures eg bronchoscopy, endoscopy, cardiac catheterization
In surgery is used to produce loss of consciousness before and during surgery
Status epilepticus(more than one seizure in 5 mins
Adverse drug reactions

• Difficulty in breathing
• Confusion and agitation
• Tremors or uncontrolled muscle movements
• Slowed heart rate
• Swelling of face, lips, tongue or throat

Common side effects

Amnesia
Headache and drowsiness
Hiccups
Nausea and vomiting
• Contraindications
Hypersensitivity to midazolam or any components of formulation
including Benzyl alcohol or any other benzodiazepine
Narrow angle glaucoma
COPD
Congestive heart failure
Chronic renal failure
Hypotension and shock
Caution in pregnant women, elderly patients and critically ill patients

Dosages
Intravenous- 0.02-0.03 mg/kg slowly over 2 mins
• Intramuscular 0.07-0.08 mg/kg
• Oral 0.2-0.5mg/kg
• Nasal 0.2-0.3mg/kg
• Rectal 0.3mg/kg
BROMAZEPAM
Drug class: Benzodiazepines
Chemical formula: C14H10BrN3O
Trade names; lexotanil, lexotan.
Mechanism of action,
Gamma aminobutyric acid positive modulator – binds to GABA-A receptor,
potentiating its inhibitory effect.
It is lipophilic. No antidepressant or antipsychotic qualities.
Pharmacokinectics,
Absorption, Taken in fasting state. Absorbed almost completely from GIT after
oral intake.
-Bioavalability-84%
Half life-1-4 hours
Metabolism-Liver (cytochrome p450 enzyems)
Elimination-via the Kidney (69%)
INDICATIONS
1.Panic disorders ( short acting)
2. Severe anxiety
3. Pre medicant prior to minor surgery
SIDE EFFECTS
Drowsiness, sedation ,ataxia ,dizziness , tremor, slurred speech.
Memory impairment- reduced ability to process environmental
information
Stopping- done gradually to avoid rebound anxiety
CONTRAINDICATIONS
1. In pregnancy ( category D)- teratogenic
2. Lactating women-sudden infant death syndrome.
Others; elderly, alcohol and drug dependent individuals.
• FORMULATIONS – Oral
• Lexotanil 3mg- 775shillings
• Dose 3 – 60 mg per day.
Encorate- Drug Overview
• Encorate (Sodium Valproate)
• Antiepileptic Drug
• Formulations available: Tablets, Syrup, Injection
Slide 2: Pharmacodynamics

• Encorate affects the body by increasing the levels of the

neurotransmitter gamma-aminobutyric acid (GABA) in the brain.
• It works by enhancing GABA-mediated inhibition of nerve
transmission.
• Key mechanisms of action include voltage-gated sodium channel
blockade and modulation of GABAergic neurotransmission.
Slide 3: Pharmacokinetics

• Encorate is well absorbed orally.

• The drug is extensively distributed throughout the body.
• Metabolism of Encorate occurs primarily in the liver.
• Elimination of the drug takes place through urinary excretion.
Slide 4: Dosage

• Lowest dose: 200 mg once daily

• Highest dose: 60 mg/kg/day (divided into two or three doses)
• Dosing may vary based on the patient's age, weight, and condition.
• Dosage adjustments are required for specific populations such as
children, elderly, and patients with hepatic impairment.
Slide 5: Uses

• Encorate is indicated for the treatment of epilepsy and seizure

disorders.
• It is used to control various types of seizures, including absence
seizures, tonic-clonic seizures, and complex partial seizures.
• It may also be prescribed for the prevention of migraines and as a
mood stabilizer in bipolar disorder.
Slide 6: Contraindications

• Encorate is contraindicated in patients with known hypersensitivity to

valproic acid or its derivatives.
• It should not be used in patients with liver disease or a history of
significant hepatic dysfunction.
• Caution is advised when prescribing to patients with a history of
pancreatitis or urea cycle disorders.
• Drug interactions may occur with other antiepileptic drugs and
medications that affect liver enzymes.
Slide 7: Fun Facts

• Encorate was first approved by the regulatory authorities in the

1970s.
• It is one of the most widely used antiepileptic drugs worldwide.
• Studies have suggested that Encorate may have neuroprotective
effects and could potentially be used in the treatment of
neurodegenerative disorders.
• Encorate has been investigated for its potential use in psychiatric
conditions such as schizophrenia and autism.
Lamotrigine
• Drug class- Anticonvulsants (Mood stabilizers)
• IUPAC name- 6-(2,3-dichlorophenyl) -1,2,4 triazine 3,5 diamine
• Pharmacodynamics- Prevents seizures and mood symptoms by stabilizing
presynaptic neuronal membranes through inhibiting voltage sensitive
sodium channels thereby modulating the release of excitatory
neurotransmitters such as glutamate that contribute to seizure activity.
• Pharmacokinetics- Usually administered orally. It is rapidly and entirely
absorbed with minimal first pass effect.
It has 98% bioavailability and about 55% protein bound.
Metabolized in the liver and excreted through urine and feces.
Indication
• Bipolar I disorder
• Generalized tonic-clonic seizures
• Partial seizures

Contraindications
• <2 years of age
• Patients with kidney, liver or heart disease
• Alcoholics
• Hypersensitivity
• Side effects- Dizziness, drowsiness, headache, vomiting, upset stomach.
• Adverse effects- Ataxia, nystagmus, increased seizures, reduced level of
consciousness, coma, delayed intraventricular conduction.
• Formulation- Tablets and oral solutions.
• Dosage- Lowest dose of 25mg PO per day and highest dose of up to 400mg
per day.
• Drug prices
Lamitical 100mg 30 tablets- Ksh 6450
Lamitor 100mg 50 tablets- Ksh 2,650
Teva lamotigrine 100mg 56 tablets- Ksh 1,630
PHENOBARBITAL
• DRUG CLASS- barbiturates (anticonvulsants)
• IUPAC name- 5 ethyl-5 phenyl- 2,4,6- pyrimidinetri-one
• Chemical formula- C12H12N2O3
Pharmacodynamics
A barbituric acid derivative that acts as a non selective CNS depressant.
Promotes binding to GABA -A receptors, and modulates Cl- currents
through receptor channels
It also inhibits glutamate induced depolarisations
PHARMACOKINETICS
Absorption
Absorbed in varying degrees following oral, rectal or parenteral
administration. The salts are more rapidly absorbed than are the acids
Oral absorption is complete but slow. Peak plasma concentration occurs
several hours
The rate of absorption is increased if the increased sodium salt is ingested as a
dilute solution or taken on an empty stomach
Distribution
Bioavailability- 24.9%
20- 45% is bound to protein
• Metabolism
Hepatic metabolism through cytochrome P450 enzymes (mostly
CYP2C19)
Half life – mean of 79 hours

Elimination
Up to 25% of a dose is eliminated by pH dependent renal excretion
Therapeutic uses
• Effective for all seizures except absent seizures
• Status epilepticus
• Insomnia
• Alcohol withdrawal syndrome
• Anxiety
• Febrile convulsions
• Hyperbilirubinemia
• Menopausal symptoms
• Withdrawal symptoms
contraindications
• Acute porphyrias
• History of alcohol abuse
• History of drug abuse
• Respiratory depression
ADVERSE EFFECTS
Sedation( tolerance developed in chronic use)
Nystagmus
Ataxia
Irritability and hyperactivity in children
Confusion in elderly
Specific side effects
a) With oral use
- Anxiety
- Hallucinations
- Hypotension
- Megaloblastic anaemia
b) With parenteral use
- Anaemia
- Duptyren’s contracture
- hypocalcemia
Formulations and dosages
• Tablets
• IV solution- in children, dilute to 20mg/ml with water for injection,
give over 20 minutes (1mg/kg/min)
• Oral solution
DOSAGES
SODIUM VALPROATE
• Also called valproic acid because it is rapidly converted to the acid
forms in the stomach.
• Available formulations include valproic acid (depakene); divalproex,a
1:1 mixture of valproic acid and sodium valproate.
PHARMACOLOGICAL ACTION
• All valproate formulations are rapidly & completely absorbed after oral
administration.
• The steady half life of valproate is about 8-17 hours, and clinically effective
plasma concentrations can be maintained with dosing one to four times a
day.
• Protein binding becomes saturated and concentrations of therapeutically
effective free valproate increase at serum concentrations above 50-100
ug/mL.
• The therapeutic effects of valproate in bipolar I disorder may be mediated
by as yet undefined effects of the drug on gamma aminobutyric acid
neurotransmitter system.
THERAPEUTIC INDICATIONS
• Bipolar I disorder
• Epilepsy
• Migraine headaches (prophylaxis)
• Schizoaffective disorder
• It is effective for the treatment of intermittent explosive disorder,
kleptomania, and other behavioural dyscontrol syndromes, particularly if
these disorders are comorbid with bipolar symptoms.
• Can effectively control physical aggression, restlessness, agitation,& to a
lesser degree, verbal aggression associated with dementia, organic brain
disease or traumatic brain injury.
CONTRAINDICATIONS
• Pregnancy
• Lactating mothers
• Bleeding disorders
• Hepatic disorders
• Renal diseases
ADVERSE EFFECTS
• CNS- seizures, increased alertness, hallucinations, aggression,
sedation
• GIT- Nausea ,vomiting, indigestion, hypersalivation, anorexia with
weight loss, abdominal cramps with diarrhoea, hepatic failure.
• Hematological -Prolonged bleeding time, leukopenia,
thrombocytopenia, bone marrow depression & anemia.
• Other-Skin rashes, transient hair loss, ammenhorea.
ADMINISTRATION
• Tablets & capsules should not be chewed. It should be swallowed
whole.
• To reduce gastric irritation administer drug with food.
• Abrupt discontinuation of the drug can lead to loss of seizure control.
• Therapeutic effectiveness is indicated by decrease in BP.
• Periodically monitor liver functions, BUN & creatinine, serum
potassium, CBC.
Diazepam (Valium)
• Chemical name: 7-chloro-1,3-dihydro-1-methyl-5-phenyl-2H-1,4-benzodiazepine-2-one
• Class: Benzodiazepine (long acting >20 hrs)
• Price: 5mg tablet = 8, ampoule = 135
• Formulations: oral tablets (2mg, 5mg or 10mg), ampoules (IV and IM) (5mg/ml) and syrup (5mg/ml).
Lowest effective dose 2mg, highest (dependent on age and specific cdns;pregnancy, lactation,
hepatic or renal impairm.
• Pharmacokinetics: absorption: oral administration, complete absorption from the gut peak plasma
concentrations within 30-90 min/IM peak conc, in >90 min; distribution: lipid soluble, highly bound
to plasma proteins, crosses BBB, bioavalability 90-100%. metabolism: in the liver to N-
desmethyldiazepam, temazepam and oxazepam; elimination: as glucuronide conjugates in urine,
prolonged terminal elimination (up to 48 hours), N-desm up to 100 hours.
• Pharmacodynamics: a positive allosteric modulator of GABA A receptor complex (potentiates the
effect), causes influx of Cl- ions in neurons leading to hyperpolarization of postsynaptic membranes,
CNS depression. Effects; anxiolytic, sedative, muscle relaxant, anticonvulsion, amnestic effects
• Indications: mngmt of anxiety disorders/short term relief of
symptoms of anxiety, alcohol withdrawal, skeletal muscle spasms
• Contraindications: pt with known hypersensitivity, paediatric pts <6
years, pts with myasthenia gravis, severe respiratory insuf, severe
hepatic insuff, sleep apnea syndrome
• Adverse effects: fatigue, drowsiness, muscle weakness and ataxia.
Anterograde amnesia. Dependency and abuse,
• Fun facts:
1) Dzm has similar sedative/hypnotic effects as barbiturates but unlike older
drugs, is a more effective anxiolytic; much less likely to result in a lethal
overdose, lower potential for abuse and dependence.
2) Concomittant use of dzm and opioids may result in profound sedation,
respiratory depression, coma and death
3) Bdzs can cause respiratory depression when given with alcohol
4) Flumazenil, a specific bdz receptor antagonist, indicated for the
complete/partial reversal of sedative effects of bdzs, including overdose
(risk of seizure during this therapy)
 PREGABALIN
• Chemical name ; 3-Isobutyl GABA
• Anticonvulsant - Gabapentinoid
Pharmacodynamics
Binds to neuronal voltage-gated calcium channels ; inhibits calcium
conductance through the channels ;reduction in glutamate release,
lowering neuronal excitability.

Pharmacokinetics
• Active absorption from GIT ; food may delay absorption
• 90% bioavalability
• Half-life 6-7 hours
• Eliminated unchanged in urine
 Clinical use
• Neuropathic pain ; diabetic neuropathy, postherpetic neuralgia, spinal cord injury
• Partial-onset seizures
• Fibromyalgia
• Anxiety disorders

Side effects
- Dizziness, fatigue
- Peripheral edema
- Weight gain
- Blurred vision
- Allergic reactions
- Poor copncentration
Contraindications
Known hypersensitivity
Use with caution in patients with;
- CHF
- bleeding disorders
- angioedema
- poor renal function

Formulations
Capsules
Tablets
Oral solution
Dosage
Start 25 - 150mg BD
Max 600mg/day

Drug prices
Gabica ksh 1,150 -1,800
Lyrica ksh1,360 -3,360
Epibalin ksh 1,080
Syngab ksh 630

* Has a risk for dependence ;esp in opioid addiction

*Withdrawal symptoms when stopped abruptly
 Zuclopenthixol
Zuclopenthixol , also known as zuclopentixol. It is classed,
pharmacologically, as a typical antipsychotic. Chemically it is a
thioxanthene. It is the cis-isomer of clopenthixol] Clopenthixol
was introduced in 1961, while zuclopenthixol was introduced in
1978 by Lundbeck.
Pharmacodynamics
Zuclopenthixol antagonises both dopamine D1 and D2
receptors, a1-adrenoceptors and 5-HT2 receptors with a high
affinity, but has no affinity for muscarinic acetylcholine
receptors. It weakly antagonises the histamine (H1) receptor
but has no a2-adrenoceptor blocking activity[citation needed.
Pharmacokinetics.
PharmacokineticsBioavailability:49% (oral)Protein
binding:98%Metabolism:Liver (CYP2D6 and CYP3A4-
mediated)Elimination half-life:20 hours (oral), 19 days
(IM)Excretion:Feces

Medical uses

Zuclopenthixol is available in three major preparations

As zuclopenthixol decanoate,(Clopixol Depot, Cisordinol Depot)
it is a long-acting intramuscular injection. Its main use is as a
long-acting injection given every two or three weeks to people
with schizophrenia who have a poor compliance with
medication and suffer frequent relapses of illness. There is
some evidence it may be more helpful in managing aggressive
behaviour.
As zuclopenthixol acetate, (Clopixol-Acuphase, Cisordinol-
Acutard), it is a shorter-acting intramuscular injection used in
the acute sedation of psychotic inpatients. The effect peaks at
48-72 hours providing 2-3 days of sedation.
As zuclopenthixol dihydrochloride (Clopixol, Cisordinol), it is a
tablet used in the treatment of schizophrenia in those who are
compliant with oral medication.
It is also used in the treatment of acute bipolar mania.
Dosing
As a long-acting injection, zuclopenthixol decanoate comes in a 200
mg and 500 mg ampoule. Doses can vary from 50 mg weekly to the
maximum licensed dose of 600 mg weekly.
In acutely psychotic and agitated inpatients, 50 - 200 mg of
zuclopenthixol acetate may be given for a calming effect over the
subsequent three days, with a maximum dose of 400 mg in total to
be given. As it is a long-acting medication, care must be taken not to
give an excessive dose.
In oral form zuclopenthixol is available in 2, 10, 25 and 40 mg tablets,
with a dose range of 20-60 mg daily.

Cost
Zuclopenthixol 100mg Accuphase - Clopixol Ksh1,600.Zuclopenthixol
Decanoate-Clopixol Depot 200mg ksh1,500.
Side Effects of Zuclopenthixol
1.Extrapyramidal symptoms (EPS): These include symptoms
such as tremors, muscle stiffness, restlessness, and involuntary
muscle movements. These symptoms are caused by the
medication's effects on the nervous system.
2.Sedation: Zuclopenthixol can cause drowsiness and sedation,
which may affect a person's ability to concentrate or operate
machinery. It is generally advised not to drive or engage in
activities requiring alertness until the effects are known.
3.Orthostatic hypotension: This refers to a drop in blood
pressure upon standing up, which can cause dizziness or
fainting. It is important to rise slowly from a sitting or lying
position to minimize this effect.
4. Anticholinergic effects: Zuclopenthixol can lead to dry mouth,
blurred vision, constipation, and urinary retention. These
effects result from the medication's impact on certain receptors
in the body.
5. Weight gain: Some individuals may experience weight gain
while taking zuclopenthixol. This can be a concern for long-term
use, as it may contribute to other health issues.
6. Endocrine effects: Zuclopenthixol may cause changes in
hormone levels, such as increased levels of prolactin. This can
lead to side effects such as breast enlargement or milk
production in both men and women.
7. Cognitive effects: Some individuals may experience difficulty
with cognitive functions, such as memory, attention, or
problem-solving abilities. These effects are generally mild and
resolve once the medication is discontinued.
Contraindications

1.Hypersensitivity
2.Central Nervous System Depression
3.Severe Cardiovascular Disorders: myocardial infarction, heart
failures, unstable angina
4.Blood Dyscrasias
5.Parkinson's Disease
6.Pheochromocytoma
PHENYTOIN
Sharon Gitari
HSM201-0146/2019
PHENYTOIN SODIUM
• Chemical name: 5,5-diphenylimidazolidine-2,4-dione
• Antiepileptic
• Formulations: oral tablets, capsules and suspension, injectabes (IV, IM
not recommended due to erratic absorption)
• Uses: Generalized tonic-clonic seizures ( previously, grand mal
seizures), status epilepticus focal seizures with impaired awareness
( formerly complex partial seizures) Temporal lobe seizures, Seizures
occurring in neurosurgery
• Used in management of acute manic episode
Ctd..
• PD: Inhibits voltage gated channels thus increasing refractory period to
prevent hyperexcitation.
• Pk: Interesting
Oral, IV
Distribution: Highly protein bound. High oral bioavailability: 70-100%
Metabolism: in the liver. Saturable enzyme metabolism> Non linear
pharmacokinetics> Small increase in dose upon saturation of hydroxylation enzymes>
High plasma concentration, risk of toxicity, Enzyme inducer: CYP2C, CYP3A, UGT
Elimination: Zero order elimination. Excreted in bile then reabsorbed in the
duodenum> liver ( Enterohepatic circulation)> Excreted in the kidneys: Glomerular
filtration & Tubular secretion
Average half life: 22 hours( 7-42), steady state achieved at 7-10 days(5-7 half lives)
• Dose: 300mg, patients should adhere strictly to prescription. Serial
monitoring of plasma levels: 10-20 micrograms/ml, Can be 100mg TD
• Fun facts:
Phenytoin is a class 1b antiarrhythmic drug, used for digoxin induced
ventricular arrythmias
Fetal hydantoin syndrome
Purple glove syndrome and IV phenytoin infusion
Contraindications: Pregnancy, Patients with DM, Hypersensitivity,
Hepatic disease, Cytopenias
• A/e
In toxic levels: cerebellar symptoms: Ataxia, Nystagmus, Vertigo, Diplopia
Gingival hyperplasia
Course facies
Hirsutism
Acne
Pancytopenia, Megaloblastic anemia,
Hyperglycemia
Osteomalaicia/rickets
Vitamin K deficiency
Teratogenic
Hyperkinesia
Phenytoin 100mg tablet> 3ksh
Phenytoin 50 mg tablet > 2ksh