PHARMACOKINETI

CS

PHARMACOLOGICA
L ACTIONS

BENZODIAZEPINES
Completely
absorbed from GIT
Erratic absorption if
IM
Can cross BBB and
placenta
Metabolized in liver

CNS
= sedation and
hypnosis, increase
duration of sleep
= decrease anxiety
(alprazolam)
= muscle relaxation
(clonazepam)
= anticonvulsant
= anterograde
amnesia
CVS
= minor effect
= preanesthetic
dose decrease : BP
= preanesthetic
dose decrease :
blood flow
= IV diazepam
increase coronary
flow
GIT
= markedly
decreased nocturnal

BUSPIRONE

CNS
= CNS depression
= sedation, ataxia,
hypnosis
Respiratory
depression
= suppress hypoxic
and chemoreceptor
response to CO2
Enzyme induction
= induce CYP450 in
liver
= diminish action of
many drugs that
depend on CYP450
eg warfarin

BARBITURATES
Rapidly absorbed
from GIT
= high lipid
solubility
Widely distributed
= redistribution to
others in short time
Metabolized in liver
Excreted via renal
route

ETHANOL
Readily absorbed
from GIT
Metabolized via
liver ans excreted
via kidney

CNS depression
= sedation and
hypnosis with
increasing dosage

MOA

USES

gastric acid
secretion
Attach at GABA at
receptor
Opening chloride
ion channels in cells
Anxiolytic
Anticonvulsant
Hypnotic
Muscle relaxant

ROA
ADVERSE EFFECTS

Oral, SL, IV, IM

Acute toxicity
= prolonged sleep
Memory impairment
= drowsiness
= confusion
= amnesia
Tolerance
Physical
dependence
Psychomotor
dysfunction
Abrupt withdrawal
= rebound insomnia

Chronic treatment
of GAD
= efficacy
comparable to Bzs
Lack anticonvulsant and
muscle relaxant
properties

SIDE EFFECTS

Tolerance

Potentiate GABA
action
Bind to receptor at
subunit
Surgical anesthesia
(Thiopentone IV)
Anti-epileptic
Sedative-hypnotic
agent
Treatment of
hyperbilirubinemia
and kernicterus
Similar to Bzs
= dizzy, drowsiness,
amnesia, tolerance,
dependence
Acute toxicity
= respiratory
depression and
circulatory shock
(fatal)
Can cross placental
barrier and excreted
in breast milk

Anxiolytic and
sedation

Oral

Chronic

Overdose coma,
severe respiratory
depression,
hypotension leading
to CVS collapse and
renal failure

DRUG
INTERACTIONS

Dependence
Withdrawal
symptoms

Potentiate effects of
CNS depressants
Cimetidine delays
metabolism of Bzs
Flumazenil (GABA
antagonist)
= IV only
= rapid onset, short
duration of action
(1/2 life 1 hour)

ANTAGONIST

consumption can
lead to liver
disease, gastritis,
and cardiomyopathy

Doesnt potentiate
effcts of CNS
depressants and
alcohol

Potentiate effects of
CNS depressant and
alcohol

Types of Bzs

Long acting
Intermediate acting
Short acting
- Diazepam
- Alprazolam
- Oxazepam
- Flurazepam
- Lorazepam
- Triazolam
During this lengthy period of time, drugs will show up in blood test and drug screens

BENZODIAZEPINES
PSYCHOLOGICAL EFFECTS
TOLERANCE

DOC fow withdrawal

is Bzs
Carbamazepines is
used as secondary
treatment in
treating convulsive
episodes
Disulfiram
= accumulation of
acetaldehyde
= flushing
= tachycardia
= nausea
Naltrexone
Acamprosate

Relaxation
Drowsy
Distraction from other problems
Physical dependence

WITHDRAWAL SYMPTOMS

EFFECTS IN OVERDOSE

Can be minimized by slowly decreasing the dose

Tachycardia
Severe headache
Tremors
Weight loss
Hyperreflexia
Agitation
Anxiety
Confusion
Unconsciousness
Respiratory depression
Collapse of heart and heart functions
CNS depression
Shallow breathing

NON BARBITURATES
Chloral hydrate
Paraldehyde
- Relatively safe
- Oral sedative dose
- Induce sleep in hour and lasts in about 6 hours
- Produces action within 15 minutes
- Used when other drugs fails
- Rarely given IV
- Disadvantages = irritant to skin and mucosa
= cyanosis
= unpleasant taste
= cough
= hypotension
- Used in emergency treatment for convulsion of tetanus,
status epilepticus
BENZODIAPINES
Clonazepam
Clorazepate
Flurazepam

Alprazolam
Lorazepam

ADVANTAGE
- Chronic therapy in seizures
-

Less potent
More slowly to be eliminated
= no rebound insomnia upon
discontinuation
DOC for panic disorders
Fewer drug interactions
Safer in patients with hepatic

DISADVANTAGE
- Disturb motor and intellectual
- Potential for dependence
- Withdrawal seizures may occur

impairments
ADVANTAGE
- Useful in long term therapy for
GAD with symptoms of irritability
- Doesnt potentiate CNS
depressants and alcohol
- Low potential for addiction
ADVANTAGE
- Rapid onset of action

BUSPIRONE
Buspirone

BARBITURATES
Phenobarbital
Pentobarbital
Thiopental

TONIC CLONIC

PARTIAL SEIZURE

Valproate
Carbamazepine
Phenytoin

Epileptic Drugs
Uses

Carbamazepine
Phenytoin
Valproate

Pharmacokinetics

Mechanism of action

CLASSIFICATION OF EPILEPSY
PETIT MAL
ATYPICAL
(ABSENCE)
ABSENCE,
MYOCLONIC
Ethosuximide
Valproate
Valproate

Phenytoin
all types of epilepsy
dose : 150-300 mg/day,
gradually increase to
maximal to 600 mg/day
Slow absorption
Inactivated by liver
microsomal enzymes
Inhibition of Na channel
function

DISADVANTAGE
- Slower onset of action
- No muscle relaxation/convulsant

DISADVANTAGE
- Tolerance
- Induce drug-metabolizing
enzymes and physical
dependence
- Severe withdrawal symptoms

STATUS
EPILEPTICUS

TOXAEMIA
(ECLAMPSIA)

Diazepam IV
Clonazepam IV
Lorazepam IV
Paraldehyde IV
Phenobarbiton
e IV

Valproate
Broad spectrum
anticonvulsant
Dose : 600 mg daily
Rapid absorption
Metabolized in liver
Excreted in urine
Similar to phenytoin
Inhibit Na channel function

MgSO4 IV

Carbamazepines
All types of epilepsy
DOC for partial seizures and
tonic clonic seizures
Dose = 100-200 BD
Slow absorption
Metabolized in liver
Excreted in urine
Similar to phenytoin
Inhibit Na channel function

= stabilizes excitables
membranes of neuronal and
cardiac cells
Adverse effects

Drug interaction

CNS
- Cerebello vestibular effects
- Ataxia
- Nystagmus
- Lethargy
- Tremor
- Dystonia
- Confusion
Long term effect
- Gum hypertrophy
- Hirsutism
- Coarsening of facial features
IV route
- Cardiac arrhythmias
- CNS depression
Overdose
- Coma
- Apnea
- Inhibition of phenytoin
metabolism
= valproate
= cimetidine
= cotrimazole
= isoniazid
= chloramphenicol

CARBAMAZEPINE
- Mania
- Trigeminal neuralgia

CNS
- Drowsiness
- Ataxia
- Diplopia
- Headache
- Nystagmus
- Reversible blurred vision
Hypersensitivity reactions
- Rash
- Dyspepsia
Others
- Water retention
- Leucopenia
- Aplastic anemia

USE OF ANTISEIZURE DRUGS IN NON-SEIZURE CONDITIONS

LAMOTRIGINE
PHENYTOIN
- Mania
- Possibly neuropathic
- Migraine
pain
- Schizophrenia
- Trigeminal neuralgia

Cbz increases metabolism of

= phenytoin
= warfarin
= theophylline
= oral contraceptives

VALPROIC ACID
- Mania
- migraine

Carbamazepine
Trigeminal neuralgia
Lamotrigine
Mania

Migraine
Phenytoin

Valproic acid

DEFINITION

ALUMINIUM SALT
- non-systemic
- widely used

MAGNESIUM SALT
- Major salts
= magnedium oxide
= magnesium
hydroxide (MOM)

CALCIUM CARBONATE
- Prompt and prolonged
effect
- Non-systemic

MOA

Form gelatinous mass

which absorbs acids
and pepsins

Can be absorbed
systemically but
rapidly excreted

ADVERSE
EFFECT

Hypophosphatemia
= absorb phosphate
= reduce phosphate
absorption
= increase phosphate
loss
Constipation
Bone fractures

Hypermagnesia
Mg intoxication
Diarrhea

On reaching acididc
environment of
stomach, insoluble
calcium carbonate
turns to calcium
chloride which can be
absorbed
Constipation
Hypercalcemia
Renal calcium stones
Milk-alkali syndrome
= hypercalcemia
+metabolic alkalosis

SODIUM BICARBONATE
- Most common home
remedies for GI upset
- Extremely effective
and prompt acid
neutralizer
- Both sodium and
bicarbonate are freely
absorbed into blood
stream

Hypertension
Systemic alkalosis

USES

IMPLICATIONS

= decrease
phosphate, decreased
calcium
= bone more brittle
Hypercalcemia
= redistribution of
calcium from bone to
blood stream
Hyperphospahtemia :
Al salts
Hypophosphatemia :
Al P
Check patients who
took high dose of
aluminium slats for
hypercalcemia and
hypophosptameia
Encourage person atr
risk of phosphate
deficiency or
osteoporosis
Dont take interacting
medications orally
within 2 hours

Antacids
Laxatives

Patient with poor renal

functions, check for
neural signs
Severe/prolonged
diarrhea may lead to
dehydration and
electrolyte imbalance
Discourage use of
Epson salt (Mg S)

Antacids but rarely

used alone, because it
can cause fecal
impaction and
constipation

Antacids
Peptic ulcer
Milk
indigestion/heartburn

Patients with GI ulcer

should not take
sodium bicarbonate
= recat with stomach
acid to form CO2 gas
= stretch ulcerated
stomach
= further tissue
damage and severe
bleeding
Avoid patients with
CVS diseases :
hypertension/heart
disease

phenothiazine
s

chlorpromazin
e

halperidol
Dopamine D2
receptor
antagonist

butyrophenon
es

domperidone

dolperidol

mtaclopramid
e (maxalon)

banzamide

DRUGS
DEFINITION

USES

PHENOTHIAZINES
Potent
Transquilizing
properties and
dopemine antagonist
will inhibit vomiting
(low, non-sedative
dose)

Gastroenteritis
Uraemia
Drug-induced
vomiting (estrogen,
tetracycline,
chemotherapy)

METACLOPRAMIDE
Phenothiazine like
action
Act on CTZ through
dopamine blockage

Oral, IM, IV
Antiemetic in
chemotherapy

ANTIHISTAMINES
Diphenhydramine
Dimenhydrmaine
Doxylamine
Cyclizine
Meclizine
Produce central
anticholinergic action
by blocking action of
H1 subtype of
histamine receptor
Prophylaxis of motion
sickness
Postoperative nausea
and vomiting

ANTICHOLINERGIC
Atropine
Scopolamine

Suppress nausea and

vomiting
Prophylaxis of motion
sickness

SIDE EFFECTS

Extrapyramidal
symptoms
Dystonia
Hypotension
Agranulocytosis

PHARMACOKINETI
CS

DRUGS

ALKALYTAING AGENTS
-

ADVERSE
EFFECTS

Nausea and vomiting

IV : local tissue necrosis

Location
- brain
- spinal cord

CNS depression
Drowsiness and
sedation
Anticholinergic action

ANTIMETABOLITES

Chlorambucil
Cyclophosphamide

IMMEDIATE
-

Receptor type
- (mu)

Extrapyramidal
symptoms
Headache,
drowsiness,
restlessness, fatigue
Rapidly and
completely absorbed
Excreted in urine

Metjotrexate
Florouracil

HORMONE AND HORMONE

ANTAGONIST
Adrenocortical steroids:
Prednisolone. Progestins
Oestrogens:
Diethylstilbesterol
Antioestrogen: Tamoxifen
Androgen : Testosterone
Antiandrogen: Flutamide

DELAYED
BM suppression
= immunosuppression
= alopecia
= GIT : stomatitis, mucositis, diarrhea
= infertility and teratogenesis
= skin : pigmentation, edema
= kidney : tubular necrosis
= lung : fibrosis
Effects
- Anelgesia
- Respiratory depression
- Euphoria

(Kappa)

(delta)

brain
spinal cord
brain

Morphine
- Pharmacological effect

Addiction
Decrease GI motility
analgesia
sedation
analgesia , little/no respiratory depression

Explanation
- Analgesia
- Euphoria
- Respiratory depression
- Cough suppression
- Pupillary constriction
- Nausea and vomiting (emesis)
- GIT symptoms
- CVS effects
= no major effects but at larger doses, hypotension and bradycardia

Uses

Route of administration

Duration
BBB

Adverse effects

Caution

Side effects

Abstinence syndrome

= respiratory depression and CO2 retention, cerebral vessels dilate and

increase CSF pressure
= contraindicated with person with brain injury or head injury
Histamine release
= urticarial, sweating, vasodilatation
= bronchoconstriction. Avoid in asthmatic patient
Analgesia
Acute pulmonary edema
Diarrhea
Cough
Oral, IM, IV , SC (Readily absorbed)
Oral = absorption from GIT slow because of significant first pass effect
60% SC injected absorbed in first 30 minutes
4-72 hours
Small percentage of morphine can cross BBB
= Fentanyl, Methadone
Respiratory depression
Vomiting
Dysphoria
Elevated intracranial pressure
Acute urinary retention
Hypotension
Pregnancy
Liver failure
Bronchial asthma
Impaired renal function
Tolerance, dependence
Respiratory depression, analgesic, euphoric, sedation (no pupil constriction
and constipation)
Abrupt discontinuation of morphine
Symptoms
= rhinorrhea
= mydriasis
= gooseflesh
= tremors
= sweating

Prevention of withdrawal

Drug interactions

= lacrimation
= chills
= muscle ache and jerks
= diarrhea
= vomiting
= yawning
= anxiety
= hostility
= hyperventilation
= hyperthermia
With anpther strong opioid drug
Codeine is not effective
Methadone DOC for maintenance programs
Rare
Enhanced by Phenothiazines and other CNS depressants

DRUGS
PHARMACOKINETICS

HYDROMORPHONE
- Oral
- Onset 15-30 minutes
- IV duration of action (3-4
hours), peak effect (30-60
minutes)

HEROIN
- Greater lipid solubility
- Cross BBB more than
morphine
- Converted to morphine in
body
- Duration of action (1/2 hour)

PROPERTIES AND
EFFECTS

Drugs
General

Potent analgesic
Morphine 8-10X
Used in surgical settings for
moderate to severe pain

Severe pain (cancer)

Naloxone
Used to reverse opioid receptors by
rapidly displacing all receptor bound
molecules
= 10 fold higher affinity for than

FENTANYL
- Oral, transdermal, IV
- Rapid onset
Oral = 7-15 minutes
transdermal = 12-17 hours
- Duration of action
Oral = 15-30 minues
transdermal = 72 minutes
- Most effective opiate
analgesic
- 80x morphine
10x hydromorphone

Naltrexone
Action similar to naloxone
Longer duration than naloxone
Used in preference than naloxone
Long onset than naloxone

Mechanism of action

Pharmacokinetics

receptors
Rapidly displace all opioid agonist
Antagonist at , , and receptors
IV injection
= onset 30 seconds
= life 30-81 minutes
No pharmacological effects in normal
individuals
No clinical effect with oral but can be
seen with IV

CLASSIFICATION OF
NSAID
-

PROSTAGLANDIN
EFFECTS
EFFECTS OF COX
INHIBITION

ASPIRIN
MOA

MARKED ANTI
INFLAMMATORY ACTION
Salicyclic acid derivatives
(aspirin)
Pyrazolone derivatives
= phenylbutazone
Acetic acid derivatives
= indomethacin
Oxicam derivatives
= piroxicam

COX -1
- Protect mucosa
- Platelet aggregation
- Vasodilatation of kidney
- Gastric ulcers
- Bleeding
- Acute renal failure

Similar to naloxone

Single dose can block effect of injected

heroin up to 48 hours
Can lead to hepatotoxicity

MODERATE ANTI
INFLAMMATORY ACTION
Propionic acid
= ibuprofen
Fenamic acid
= mefenamic acid
Non acidic
= nabumetone

COX
-

EXPLANATION
- Inhibitors of COX enzymes

MILD ANTI INFLAMMATORY

ACTION
Aniline derivatives
= paracetamol

2
Inflammation of peripheral injury site
Modulate pain perception
Promote fever
Reduce inflammation
Reduce pain
Reduce fever

PHARMACOLOGICAL EFFECT

USES

PHARMACOKINETICS

REYES SYNDROME

DOSAGE
ADVERSE EFFECT

Anti-inflammatory = inhibits but dont stop progress

Analgesic = blocking PGE-2 synthesis, repress sensation of pain
Antipyretic = blocking PGE-2 synthesis, lowers body temperature by
increasing heat dissipation. No effect on normal body temperature
Respiratory action
= therapeutic : increase alveolar respiration
= higher dose : hyperventilation and respiratory alkalosis
= toxic : central respiratory paralysis and respiratory alkalosis
GIT effects : inhibits formation of prostanoids, increased gastric acid
and mucus
Kidney : decrease PG synthesis, retention of sodium and water
= edema, hyperkalemia, interstitial nephritis
Platelets : decrease in TXA2 production, reduced antiplatelet effect,
prolonged bleeding time
Anti-inflammatory
Analgesic
Antipyretic
External applications
CVS : reduce risk of TIAs, MIs, unstable angina pectoris, stroke and
death
After oral, absorption partly absorbed from stomach, mostly from
upper small intestine
Rectal is slow and unreliable
Avoided in children and teenagers : Reyes Syndrome
Can cross placenta and BBB
Fatty change in liver and edematous encephalopathy following aspirin
use, 3-5 days later
Affects children between 6-15 yo
Etiology uncertain
Precede by mild upper respiratory tract/varicella/influenza
Aspirin administration is not toxic
25% progress to coma
325 mg 4x daily : analgesic
325 mg 10-12 per day : anti-inflammatory
GIT
= epigastric distress
= GI bleeding

Drugs
Properties

Type

= nausea
= vomiting
Bleeding
= prolonged bleeding time
Respiration
= depression and metabolic acidosis at toxic dose
Hypersensitivity
= urticarial, bronchoconstriction, angioedema, anaphylactic shock
Reyes syndrome
= fatal, hepatitis with cerebral edema

Acetaminophen (PAP)
By blocking PG synthesis in CNS
= antipyretic
= analgesic
Less effect on COX in
peripheral tissues, weak
anti-inflammatory action Does not alter platelet
function/increase
clotting time
Not considered NSAIDs

Location

Ibuprofen
Anti-inflammatory,
analgesic and antipyretic
Alter platelet function
and prolong bleeding
time
Widely used for
RHEUMATIC ARTHRITIS
and OSTEOARTHRITIS
because effects are less
intense than aspirin

Function

Celecoxib
COX-2 inhibitor
Uses = RA, osteoarthritis
= acute to
moderate pain
Does not inhibit platelet
aggregration and does
not increase bleeding
time
Similar efficacy to
NSAIDs in treatment of
pain and CVS events

H1 histamine receptor

Causes vasodilation, bronchoconstriction,

bronchial smooth muscle contraction,
separation of endothelial cells (responsible
Found on smooth muscle, endothelium, and
for hives), and pain and itching due to
central nervous system tissue
insect stings; the primary receptors
involved in allergic rhinitis symptoms and
motion sickness.

H2 histamine receptor

Located on parietal cells

Primarily stimulate gastric acid secretion

H3 histamine receptor

Found on central nervous system and to a

lesser extent peripheral nervous system
tissue

Decreased neurotransmitter release:

histamine, acetylcholine, norepinephrine,
serotonin

H4 histamine receptor

Found primarily in the basophils and in the

bone marrow. It is also found on thymus,
small intestine, spleen, and colon.

Plays a role in chemotaxis.

LOCALIZED ALLERGIC REACTION

- Release of histamine is slow enough to be inactivated
before entering bloodstream
H1 RECEPTOR BLOCKER
TYPES
ACTION
PHARMACOKINETICS

FULL BLOWN ANAPHYLAXIS RESPONSE

- Release of histamine is too fast enough for inactivation
to be efficient

EXPLANATION
1st gen
2nd gen
Block histamine receptors from histamine
Well absorbed after oral administration
Distributed in all tissues
Plasma half-life = 4-6 hours
Onset = 1-3 hours

THERAPEUTIC USES

OTHER CLINICAL USES

ADVERSE EFFECTS

DRUG INTERACTIONS
OVERDOSE

Duration of action : 24 hours

Allergic and inflammatory conditions
= not for bronchial asthma
Motion sickness and nausea
= diphen
= dimen
= cyclizine
= meclizine
Somnifacients
= diphen
= doxylamine
Others
= rhinitis
= conjunctivitis
= urticarial
= angioedema
= puritus
= anaphylaxis
Rhinitis
Conjunctivitis
urticaria
puritus
Anaphylaxis
Low specificity
React with muscranic
Alpha-adrenergic = hypotension, dizziness, reflex tachycardia
Serotonin = appetite
Cholinergic = dry mouth, urinary retention, sinus tachycardia
Can potentiate with all CNS depressants including alcohol
Hallucinations, excitement, ataxia, convulsions

DIFFERENCES
1st GEN H1
- 3-4 daily doses

2nd GEN H1
- 1-2 times daily

Cross BBB (lipophilic, low MW, lack recog of Pglycoprotein efflux pump)
Potentially cause side-effects
Toxicity are possible
Lethal dose identified for yound children
No randomized, double-blind placebo-controlled trials in
children

SYMPHATETIC NERVOUS SYSTEM

- Adjust in response in stressful situations
- Increased heart rate and BP
- Mobilize energy stores of body
- Increase blood flow to skeletal muscles and heart
- Pupil and bronchioles dilatation
- Stimulates GI motility and secretion
ACETYLCHOLINE
ACTIVITY

Doesnt cross BBB

Does not cause relevant side effects

No reports of serious toxicity
Do not cause fatality
Got

PARASYMPHATETIC NERVOUS SYSTEM

- Maintains essential bodily functions
- Dominant over sympathetic in rest and digest
situations
- Never discharges as complete system

EXPLANATION
Mediates transmission of nerve impulses across autonomic ganglia in both symphatetic and
parasymphatetic

TYPE
PHARMACOLOGICAL
EFFECT

OTHER CHOLINERGIC
AGENT

PILOCARPINE

ACTIVITY
PHARMACOLOGICAL EFFECTS

ADVERSE EFFECTS

Antagonist

Has muscarinic and nicotinic activity

Cholinergic, parasympathomimetic
Decrease in BP
GIT
= increase salivary secretion, intestinal secretions and motility, bronchiolar secretions
Genitourinary tract
= increases tone of detrusor muscle, expulsion of urine
Eye
= stimulates ciliary muscle contraction and pupillae schinter causing miosis
Bethenecol = lack nicotinic but strong muscarinic (intestinal motility and detrusor)
Pilocarpine = penetrate to CNS at therapeutic doses, muscarinic activity, used primarily in
opthmalogy
Carbachol
Therapeutic uses
= lowering intraocular pressure of both wide and narrow angle glaucoma
= promote salivation in patients with head and neck irradiation
Adverse effects
= CNS disturbances
= profuse sweating and salivation
ATROPINE
SCOPOLAMINE
BOTH INHIBIT MUSCRANIC RECEPTORS IN CNS (ANTIMUSCRANICS)
- Block M1, M2, M3
- Eye : persistent mydriasis
- GIT : reduced motility
- Reduced secretions
- Dry mouth
- Tachycardia
- Blurred vision
- CNS
= restlessness, confusion,
hallucinations, delirium
- Low doses of physostigmine