Ali AbdelWahab, Medical Pharmacology & Therapeutics
MEDICAL PHARMACOLOGY
&
THERAPEUTICS
FOR
MEDICAL STUDENTS
BY
ALI ABDELWAHAB
PROFESSOR OF MEDICAL PHARMACOLOGY
FACULTY OF MEDICINE
BENI SUEF UNIVERSITY & CAIRO UNIVERSITY
2022
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Ali AbdelWahab, Medical Pharmacology & Therapeutics
Chapter 9:
CENTRAL NERVOUS SYSTEM
Intended learning outcomes (ILOs):
By the end of this chapter, the student should be able to:
1. Classify antiparkinsonian drugs and their actions
2. Distinguish between levodopa, bromocriptine, COMT inhibitors and
anticholinergics regarding their preference use and adverse effects
3. Classify antipsychotics "neuroleptics" and their mechanisms of actions
4. Compare between typical and atypical antipsychotics
5. Classify antidepressants and their mechanisms of actions
6. Compare between SSRIs, TCAs and MAO inhibitors
7. Describe main mode stabilizers
8. Describe the actions and side effects of main CNS stimulants
9. Describe drugs affecting size of pupil and their mechanism of action
10. Discuss drug treatment of glaucoma and common eye diseases
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Ali AbdelWahab, Medical Pharmacology & Therapeutics
DRUG THERAPY OF PARKINSONISM
Parkinsonism (paralysis agitans) is a disease of basal ganglia characterized by
bradykinesia (mask face), muscle rigidity, static tremors (pill-rolling
movement), salivation and depression.
It is usually idiopathic, but may result from cerebral ischemia, viral
encephalitis, or iatrogenic from reserpine or antipsychotic D2-blockers
There is imbalance between dopamine and acetylcholine in the basal ganglia
with loss of dopaminergic neurons in substantia nigra that normally inhibit
excitatory cholinergic cells in the corpus striatum, and treatment aims to
restore the balance between these neurotransmitters.
Anti-parkinsonian drugs
IDopaminergic drugs
1- L-Dopa ± dopa decarboxylase inhibitors (PDDI)
Carbidopa & Benserazide: enhance L-dopa effect & ↓ its peripheral toxicity
2- COMT inhibitors:
Entacapone (peripheral COMTI), Tolcapone (act CNS & periphery but hepatotoxic)
They decrease metabolism of L-dopa & dopamine, decrease 3OMD that compete
with L-dopa for CNS uptake
3- MAO-B inhibitors:
Selegiline: inhibit degradation of dopamine, enhance L-dopa & ↓disease progression
4- Dopamine agonists:
- Ergot derivatives: Bromocriptine, Pergolide, Quinagolide
- Non- ergots: Pramipexole, Ropinirole, Rotigotine
5- Amantadine
II- Central Anti-cholinergic drugs:
They improve tremors, rigidity, salivation & little effect on bradykinesia
Used as add-on with L-dopa or in iatrogenic parkinsonism by anti-psychotics
Side effects: drowsiness, confusion, agitation, hallucination, blurred vision,
urine retention, constipation, (CI in glaucoma & prostatic hypertrophy)
1- Natural belladonna alkaloids:
Atropine, Hyoscine
2- Synthetic atropine substitutes:
Benztropine, Benzhexol (Trihexyphenidyl), Biperiden, Caramiphen
3- Anti-histaminics (with anti-M activity): Orphenadrine, Diphenhydramine
4- Ethopropazine; Phenothiazine, potent anti-M, effective in oculogyric crisis
III- Other new treatments
-DOPS (dihydroxyphenylserine): precursor of NA may help severe cases
-GM1 ganglioside, Urocortin: may ↑dopamine level & neuron regeneration
-Transplantation of dopaminergic tissue from adrenal or fetal substantia nigra
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Ali AbdelWahab, Medical Pharmacology & Therapeutics
L-DOPA
Levo-Dopa is the precursor of dopamine that pass BBB to be converted to
dopamine and increase its activity in basal ganglia to correct all symptoms of
parkinsonism esp. bradykinesia
Kinetics:
L-dopa is administered orally to be absorbed by an active process in the
intestine (↓by some amino acids in food), peak conc. in 1-2h., t1/2=1-3h.
- Most (>95%) of ingested l-dopa is metabolized in peripheral tissues by:
- DD (dopa decarboxylase) to dopamine, which cannot pass the BBB.
[Pyridoxine (vit. B6) activate peripheral DD, so decrease the efficacy &
increase toxicity of L-dopa]
- COMT to 3-O-methyl dopa (3OMD) that compete with L-dopa for
active uptake to the CNS
- Only 1-3% of ingested l-dopa (prodrug) reaches CNS to be metabolized by
central DD into dopamine (active) to produce the therapeutic effect, then
metabolized by MAO-B & COMT enzymes, to be excreted as inactive metabolites
L-dopa
100%
70%
Metab.
in GIT
L-dopa+carbidopa
1-3%
CNS
(Efficacy)
28%
Metab.
in peripheral tissues
(DD & MAO) (DD & COMT, toxicity)
100%
40%
10%
CNS
(Efficacy)
50%
Metab. Metab.
in GIT in periphery
(DD & MAO) (DD & COMT, toxicity)
Dynamics:
-Antiparkinsonian effect by increasing brain dopamine that stimulate D2
receptors in basal ganglia, to improve all manifestations especially
bradykinesia > tremors. Best results in first few years before wearing-off.
-Efficacy & brain level of L-dopa can be increased by adding:
1- Peripheral DD inhibitor (not pass BBB) as carbidopa or benserazide
- Carbidopa (25mg) + L-dopa (100 or 250mg) = Sinemet
- Benserazide (25mg) + L-dopa (100mg) = Madopar
2- COMT inhibitor as tolcapone (hepatotoxic) or entacapone
3- MAO-B inhibitor as selegiline (deprenyl) (slow disease progression)
Side effects of L-dopa:
1- Fluctuation of response (on-off phenomenon); may be reduced by use of drug
holidays, use dopamine agonists & reserve l-dopa for late severe disease
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Ali AbdelWahab, Medical Pharmacology & Therapeutics
2- CNS effects: dyskinesia (chore & athetosis), psychological disturbances,
hallucination, insomnia, anxiety, agitation & mood changes (ttt by clozapine)
3- CVS effects: tachycardia, arrhythmia, postural hypotension or hypertension
4- GIT effects: anorexia, nausea, vomiting, peptic ulceration (ttt by domperidone)
5- Other effects: mydriasis, increase IOP, hemolysis, brown secretion
Contraindications:
1- Psychosis
2- Glucoma
3- Peptic ulcer
4- Cardiac disease
5- Melanoma
6- With MAO-A inhibitors
DI:
Favorable DI: (increase brain level & activity of L-dopa)
1- Peripheral DD inhibitor (not pass BBB) as carbidopa or benserazide
2- COMT inhibitor as tolcapone (hepatotoxic) or entacapone
3- MAO-B inhibitor as selegiline (deprenyl) (slow disease progression)
Unfavorable DI:
1- With non-selective MAO inhibitors: severe hypertension
2- With pyridoxine (vit B6): enhance peripheral decarboxylation of l-dopa
3- With Dopamine blockers (antipsychotis, antiemetics): decrease l-dopa effect
Amantadine (Symmetrel)
Anti-viral agent used in prophylaxis of influenza A2 infection
Useful in parkinsonism by releasing dopamine & decreasing its reuptake, but
its effect is short for only few weeks, 100mg twice/day orally
Side effects: -CNS: insomnia, irritability, confusion, hallucination
-CVS: hypotension, CHF, peripheral edema
-GIT: gut upset
Contraindication: CHF & epilepsy
Bromocryptine (Parlodel)
Derivative of ergot alkaloids
Absorbed orally, metabolized in liver and excreted in bile & feces, long t1/2
Direct agonist on D2-R & partial agonist on D1-R; may ↑dopamine levels
Uses: - Parkinsonism, 2.5mg twice daily orally, up to 30mg/day
- Suppression of lactation
- Hyperprolactinemia and galactorrhea-amenorrhea syndrome
- Acromegaly
Side effects:
1- CNS effects: dyskinesia, psychological disturbances, hallucination
2- CVS effects: arrhythmia, postural hypotension, digital vasospasm,
erythromyalgia (red, hot, tender, swollen feet)
3- GIT effects: anorexia, nausea, vomiting, dyspepsia, constipation
Contraindications: psychosis, recent MI, PVD, peptic ulcer, pregnancy
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Ali AbdelWahab, Medical Pharmacology & Therapeutics
N.B.: drug treatment of parkinosn's disease:
- Mild symptoms: conserve, selegiline may decrease disease progression
- Significant symptoms: L-dopa combinations as Sinemet, entacapone, amantadine,
- Severe disease & response fluctuation: add bromocriptine or pergolide,
antimuscarinics, physiotherapy
- Drug-induced parkinsonism: antimuscarinic agents
N.B.: Drugs contraindicated in parkinsonism:
1- D2-R blockers: phenothiazines, butyrophenones, metoclopramide
2- Reserpine (deplete dopamine stores)
3- α- methyl dopa (decrease dopamine synthesis)
4- Cholinomimetics (lipid sol, pass BBB): pilocarpine, physostigmine
5- Destruction of negrostriatal dopamine neurons by MPTP → MPP* →
frozen addict syndrome
N.B.: Treatment of other movement disorderes:
- Familial tremors:
- Propranolol
- Chorea & Ballismus: - Dopamine blockers; haloperidol,
- Reserpine, tetrabenazine,
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Ali AbdelWahab, Medical Pharmacology & Therapeutics
PSYCHOTROPIC DRUGS
Drugs that affect psychology and behavior, classified into:
I- Tranquilizers (Psycholeptics):
- Minor tranquilizers (Anxiolytic-sedatives) e.g. diazepam
- Major tranquilizers (Antipsychotics) e.g. chlorpromazine
II- Antidepressants (Psychoanaleptics, Mood-elevating) e.g. TCA
III- Mood-stabilizing agents useful in mania e.g. lithium
IV- Psychomotor stimulants (↑alertness) e.g. amphetamine
V- Psychotomimetics (Hallucinogenics) e.g. LSD
ANTI-PSYCHOTICS
(NEUROLEPTICS, MAJOR TRANQUILIZERS)
Drugs used in major psychotic disorders as schizophrenia
*Schizophrenia is a mental illness characterized by:
- Positive signs e.g. hallucinations, delusions and abnormal behavior
- Negative signs e.g. society withdrawal, lack of emotion & motivation
Psychosis may be due to disturbed neurotransmitter levels in the hypothalamus
and mesolimbic system especially increased dopamine and serotonin activity.
All anti-psychotics are potent blockers of dopamine &/or 5-HT receptors.
Reserpine was used as antipsychotic by depleting monoamines stores.
Classification of anti-psychotic drugs:
- Typical Antipsychotics:
- Phenothiazines: Chlorpromazine, Thioridazine, Trifluoperazine, Fluphenazine
- Thioxanthenes: Thiothixene, Chlorprothixene
- Butyrophenones: Haloperidol, Droperidol
- Atypical Antipsychotics:
Clozapine, Pimozide, Sulpride, Remoxipride, Resperidone, Olanzapine,
Quetiapine, Loxapine, Sertindole, Molindone
Chlorpromazine (Largactil)
Kinetics:
-Administered orally & IM; low oral bioavailability due to 1st pass effect
-Distributed all over the body, 95% protein-bound; Vd= 7 L/kg, t1/2= 10-24 h.
-Metabolized in liver to many active& inactive metabolites, then excreted
Dynamics:
1- CNS:
Potent blocker of dopamine (D2) receptors in brain areas:
- D2 block in limbic system & cortex —→ Anti-psychotic effect
- D2 block in basal ganglia —→ Extrapyramidal effects & worsen parkinsonism
- D2 block in hypothalamus —→ Hypothermia, ↑Prolactin & ↑appetite
- D2 block in CTZ—→ Antiemetic in all vomiting except motion sickness
- Sedation, potentiate CNS depressants, lower seizure threshold
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Ali AbdelWahab, Medical Pharmacology & Therapeutics
2- Endocrine effects:
- ↑Prolactin —→ gynecomastia in males & galactorrhea in females
- ↓Gonadotrophins (FSH&LH) —→ amenorrhea & infertility
- ↓ACTH & Growth hormone
- ↑MSH & aldosterone
3- Autonomic effects:
- Potent; anti-dopamine (D2>D1), anti-serotonin (5-HT2), α-blocker
- Weak anti-muscarinic, anti-histaminic (H1), anti-nicotinic
4- Skeletal muscle relaxant effect; peripheral & central
5- Local anesthetic and direct cardiac depressant effect
6- CVS;
- Hypotension & Postural hypotension due to;
↓VMC, ganglion block, α-block, direct VD, direct cardiac depression
- Tachycardia (reflex & anti-M), cardiac depression, prolonged QT interval
Therapeutic uses:
I- Psychiatric uses:
Psychosis; schizophrenia, mania, Huntington chorea & Tourette's syndrome
II- Non-psychiatric uses:
1- Pre-anesthetic medication & neurolept-analgesia
2- Hypothermic agent in cardio-, neuro-& plastic surgery (lytic cocktail)
3- Anti-emetic effect in all types of vomiting except motion sickness
4- Intractable hiccough
5- Anti-pruritic for persistent pruritis
Adverse effects:
1- Neurological side effects:
-Extrapyramidal manifestations; akathisia (motor restless), acute dystonia
(muscle spasm), parkinsonism
-Tardive dyskinesia, abnormal movement due to upregulation of D2 R. on long use
-Neuroleptic malignant syndrome, rare idiosyncratic reaction, ttt: cooling & dantrolene
2- Sedation, pseudodepression, confusion, seizures
3- Postural hypotension, failure of ejaculation (α-block)
4- Dry mouth, blurred vision, constipation (atropine-like)
5- Endocrine effects; amenorrhea, galactorrhea, infertility, gynecomastia,
6- Weight gain due to excess food intake
7- Allergic obstructive jaundice
8-Allergy, dermatitis, photosensitivity, agranulocytosis
9- Opacities and deposits of cornea & lens
10-Teratogenesis (CI during pregnancy)
Drug interactions:
1- Potentiate (additive effect) other drugs:
Sedatives, hypotensives, α-blockers, anticholinergics, muscle relaxants
2- Antagonize: dopamine agonists, guanethidine (inhibit neuronal uptake)
3- Reverses the hypertensive effect of adrenaline (α-block)
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Ali AbdelWahab, Medical Pharmacology & Therapeutics
Other Anti-psychotic drugs
Typical antipsychotics:
- Thioridazine: (metabolized to active mesoridazine)
Phenothiazine similar to chlorpromazine but:
-Less antiemetic, less extrapyramidal effects, potent antimuscarinic
-Cause retinal deposits & cardiotoxicity (VT)
- Trifluoperazine:
Phenothiazine similar to chlorpromazine but:
More potent antipsychotics with more extrapyramidal manifestation
- Thioxanthenes: Thiothixene
Antipsychotic similar to chlorpromazine, but less autonomic effects
- Butyrophenones: Haloperidol & Droperidol
More potent antipsychotics, antiemetic & extrapyramidal effects
Uses: -Antipsychotic in schizophrenia
-Haloperidol is useful in children with Huntington's chorea
-Droperidol is used with fentanyl (Thalamonal) in neurolept-analgesia
Atypical Antipsychotics:
They block dopamine & 5-HT receptors, more effective in resistant cases of
schizophrenia & can improve negative signs than typical agents; with less
extrapyramidal, endocrine & autonomic side effects.
- Clozapine (Block D4=α1>5-HT2>H1>M>D2=D1), causes agranulocytosis & seizures
- Risperidone (Block D2, D4 & 5-HT2)
- Olanzapine (Block 5-HT2>D2)
- Quetiapine (5-HT1A partial agonist)
- Aripiprazole (D2 and 5-HT1A partial agonist)
- Pimozide (Long-acting D2-blocker)
- Sulpride (Block mainly presynaptic D2-R)
- Remoxipride (Block both D2 & D3)
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Ali AbdelWahab, Medical Pharmacology & Therapeutics
ANTI-DEPRESSANTS (PSYCHOANALEPTICS)
(Treatment of Affective (Mood) Disorders)
*Depression:
Depression is a heterogenous psychic disorder with diverse depressive
symptoms as lack of motivation, tension, anxiety, lost libido, insomnia or
abnormal sleep. It can be classified into:
-Reactive depression: mild form secondary to bad life events, diseases or
drugs. It usually recovers spontaneously or by reassurance
-Endogenous (psychic) depression: spontaneous depressive symptoms, caused
by disturbed neurotransmitter activity in the brain. It tend to recur and usually
require by anti-depressant drugs or electro-convulsive therapy
-Bipolar affective disorder: cyclic episodes of depressed mood alternating
with attacks of mania (manic-depressive illness). It is treated by moodstabilizing agents as lithium ± antidepressants or antipsychotics
Types of Anti-depressant drugs:
1- Monoamine oxidase inhibitors (MAOI)
2- Tricyclic antidepressants (TCA)
3- Selective serotonin reuptake inhibitors (SSRI) (most prescribed)
4- Atypical antidepressants
N.B.: Monoamine oxidase enzyme (MAO)
MAO is intracellular enzyme found in mitochondria of nearly all tissues
There are two types of MAO:
- MAO-A: - Metabolizes NA, 5-HT & tyramine
- Selective inhibitors e.g. clorgyline, used as antidepressants
- Moclobemide is a reversible inhibitor of MAO-A (RIMA)
- MAO-B: - Metabolizes dopamine & phenylethylamine
- Selective inhibitors e.g. selegiline, used as antiparkinsonian
MONOAMINE OXIDASE INHIBITORS (MAOIs)
They are classified into:
-Non-selective MAO inhibitors:
-Hydrazine group: Iproniazid, Nialamide, Isocarboxazide, Phenelzine
-Non-hydrazine group: Tranylcypromine, Pargyline
-Selective MAO-A inhibitors: Clorgyline, Moclobemide (RIMA)
Kinetics:
They are rapidly absorbed orally, metabolized in liver (slow or rapid
acetylation of hydrazine group) & excreted in urine as metabolites
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Ali AbdelWahab, Medical Pharmacology & Therapeutics
Dynamics:
They are non-selective irreversible inhibitors of MAO enzymes esp. hydrazines
leading to accumulation of monoamines (NA & 5-HT) in cytoplasm of presynaptic
neurons with increased transmitter release, down-regulation of β-, α2- & 5-HT2receptors; & decreased excretion of VMA & 5-HIAA in urine
-The antidepressant & mood-elevating effect appears after 2-3 weeks &
persists for 2-3 weeks after stopping drug use
-Tranylcypromine can release NA and elevate blood pressure
-Pargyline has antihypertensive & antianginal effect
Therapeutic uses:
-Psychic depression especially severe atypical depression associated with
neurotic symptoms, anxiety, phobias & severe facial pain
Side effects & toxicity:
1- CNS: excitation; agitation, tremors, insomnia, delirium, convulsions
2- CVS: postural hypotension, hypertensive reactions
3- Hepatotoxicity & jaundice (hydrazines)
4- Appetite stimulation & weight gain
5- Weak atropine-like effects; constipation, dry mouth
6- Optic nerve damage, rash, leucopenia
Drug interactions:
1- Cheese reaction: Food containing tyramine as cheese, yoghourt, beans,
bear, yeast extract → hypertensive crisis with MAO inhibitors
2- Hypertensive reactions with: -Indirect sympathomimetics as ephedrine
-Reserpine (Reversal)
-Guanethidine
-Methyl-dopa & L-dopa
3- HME inhibition & potentiate action of drugs as:
-TCA → toxicity (atropine-like toxicity)
-SSRI → serotonin syndrome (hyperthermia, rigidity, hypotension, coma)
-Morphine, meperidine, barbiturates, aminophylline, tolbutamide, .
TRICYCLIC ANTI-DEPRESSANTS (TCA)
They are chemically related to phenothiazines & carbamazepine
-Imipramine
-Desipramine
-Clomipramine
-Amitriptyline
-Nortriptyline
-Protriptyline
-Doxepin
-Amineptine
Kinetics:
They are incompletely absorbed orally with significant first pass effect, bound
to plasma proteins, highly lipid-sol. & widely distributed, metabolized in liver
to active metabolites (Imipramine → Desipramine, Amitriptyline →
Nortriptyline) & excreted in urine as inactive conjugated metabolites
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Ali AbdelWahab, Medical Pharmacology & Therapeutics
Dynamics:
They block neuronal reuptake1 of monoamines (NA & 5-HT) (cocaine-like)
leading to their accumulation in synapses facilitating transmission, with downregulation of β-, α2-, 5-HT2- receptors & up-regulation of α1-R
1- The antidepressant & mood-elevating effect appears after 2-3 weeks & persists
for 2-3 weeks after stopping drug use
2- Sedation, most with amitriptyline & doxepin, less with desipramine
3- Anti-cholinergic (atropine-like) activity
4- Anti-histaminic, H1- & H2- blocking effect
5- Anti-serotonin
6- Alpha1-blocking effect
7-CVS: postural hypotension, tachycardia, arrhythmia, cardiac depression
Therapeutic uses:
1- Psychic depression
2- Phobias & acute panic disorders
3- Obsessive compulsive neurosis
4- Nocturnal enuresis & urinary incontinence
5- Chronic pains & migraine prophylaxis
6- Others: anorexia nervosa, bulimia, cocaine withdrawal & ADHD
Side effects & toxicity:
1- CNS: -Sedation, fatigue, confusion, delirium, excitation & convulsions
2- CVS: Postural hypotension, tachycardia, arrhythmia, cardiac damage
3- Atropine-like toxicity; dry mouth, blurred vision, urine retention &
constipation (CI; glaucoma & prostatic enlargement)
4- Allergic obstructive jaundice
5- Appetite stimulation & weight gain
6- Agranulocytosis, rashes
*Acute toxicity of TCA: (common & serious)
Manifestations: Agitation, delirium, irritability, hyperreflexia, seizures, apnea,
metabolic acidosis, cardiac arrhythmias, shock & coma
Treatment: -Stomach wash & activated charcoal
-Supportive care for pH & electrolyte imbalance (NaHCO3)
-For arrhythmias: NaHCO3, phenytoin (ttt arrhythmia & seizures)
-Diazepam for convulsions, & other symptomatic treatment
-Physostigmine IV to correct the anti-muscarinic effects (?)
Drug interactions:
1- Potentiate other drugs: - Sedatives & alcohol
- Anti-cholinergics
- Sympathomimetic catecholamines (↓uptake)
2- Antagonize hypotensive effect of: -Guanethidine (↓uptake)
-Methyl-dopa & clonidine (↓α2-R)
3- TCA with MAOI, cause atropine-like toxicity & convulsions
4- Imipramine is a HME inducer & increase metabolism of other drugs
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SELECTIVE SEROTONIN REUPTAKE INHIBITORS (SSRI)
Fluoxetine, Fluvoxamine, Paroxetine, Sertraline, Citalopram, Escitalopram
They inhibit serotonin reuptake, increasing its level, leading to mood elevation &
antidepressant effect. The antidepressant & mood-elevating effect appears after 2-3
weeks & persists for 2-3 weeks after stopping drug use.
They are safer than TCA with no anti-cholinergic effect, no cardiotoxicity, no
hepatotoxicity, no weight gain, & little drug interactions.
Uses: - Psychic depression
- Panic disorders
- Obsessive compulsive disorders
- Eating disorders e.g. Bulimia nervosa
Side effects: - Anorexia, nausea, diarrhea & weight loss
- Anxiety, insomnia, mania, headache
- Aggression, violence & suicidal tendency
DI: - They are potentiated by MAOI → serotonin syndrome
- Fluoxetine is HME inhibitor and potentiate other drugs
ATYPICAL ANTIDEPRESSANTS
They are effective in depression as TCA, but:
- Have more rapid onset & may be effective in resistant cases
- Produce less sedation, less autonomic effect, less toxicity on overdose
Selective Serotonin/NA Reuptake Inhibitors (SNRI):
1-Venlafaxine
Selective NA/5-HT reuptake inhibitor (inhibit 5HT> NA) with more rapid effect.
2-Desvenlafaxine
Synthetic form of the active metabolite of venlafaxine with less side effects.
3- Duloxetine
Selective SNRI, useful in depression, urinary incontinence, anxiety & pain disorders.
4- Milnacipran
Selective SNRI, useful in fibromyalgia.
Selective NA Reuptake Inhibitors:
1-Bupropion
Inhibits NA/Dopamine reuptake (NDRI) & nicotinic antagonist.
Used for smoking cessation (SR form), ADHD, sexual dysfunction & obesity.
2-Maprotiline
Inhibit uptake of NA, cause cardiotoxicity & seizures on overdose (as TCA).
-Amineptine
TCA, inhibit dopamine uptake only, rapid onset, no anti-M, dependence
-Nomifensine
Inhibit uptake of NA & dopamine
3-Atomoxetine & Reboxetine:
Selective NA reuptake inhibitors recently used for treatment of ADHD in children.
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Ali AbdelWahab, Medical Pharmacology & Therapeutics
Monoamine Receptor Antagonists:
1-Mirtazapine
Blocks a-2, 5-HT2c and 5-HT3 receptors increasing release of NA & 5-HT.
2-Trazodone
Blocks 5-HT2A, 5-HT2c increasing release of 5-HT & weak inhibitor of 5-HT uptake.
3-Mianserine
Block presynaptic α2-R increasing NA release, cause sedation
ANTI-MANIA & MOOD-STABILIZING DRUGS
Mania is a psychic disorder characterized by impulsive actions, self-confidence,
delusions, irritability, aggression & abnormal behavior. Periods of mania usually
alternate with periods of depression in the bipolar affective disorder. It is treated by
mood-stabilizing agents ± antidepressants or neuroleptics
Mood-stabilizing drugs useful in treatment of mania include;
-Lithium carbonate, Carbamazepine, Sodium valproate, Lamotrigine
LITHIUM
Lithium is an endogenous monovalent cation with unknown physiological function
Kinetics:
Lithium carbonate is absorbed orally, widely distributed & eliminated by renal
excretion (therapeutic level=1-1.5 meq/L)
- Lithium clearance increase by;
Osmotic diuretic, Na load, urine alkalinizer NaHCO3, acetazolamide, triamterene
- Lithium clearance decrease by;
Thiazides & loop diuretics, spironolactone, NSAIDs, hyponatremia
Dynamics:
Lithium has a mood-stabilizing effect, by undefined mechanism, but effects include:
Decreased cellular content of phosphatidyl inositol, ↓nerve conduction,
↓release of neurotransmitters NA, 5-HT, dopamine
Uses: (dose= 1.5-2.5 g/day)
- Acute mania, but has slow onset (5-6 days), [± neuroleptic]
- Prophylaxis of manic-depressive disorder [± antidepressant]
- Management of aggressive &violent behavior in prisoners
Side effects:
1- CNS: ataxia, tremors, confusion, fatigue, weakness, convulsions, coma
2- CVS: bradycardia, arrhythmias, hypotension
3- Thyroid dysfunction, hypothyroidism & goiter
4- Kidney: polyurea, thirst (antagonize ADH on renal tubule, nephrogenic DI)
5-Skin rash, leukocytosis, edema, wight gain
6- GIT: anorexia, nausea, vomiting, diarrhea
7- Teratogenesis & affect suckling baby (CI during pregnancy & lactation)
7- Acute toxicity if plasma level > 2-2.5 meq/L
Treated by osmotic diuretics, Na+HCO3 & dialysis in severe cases
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C.N.S. Stimulants
Spinal Cord
Drugs that stimulate brain centers to increase mental and physical activity.
They increase alertness, energy, rise BP & respiratory rate, depress appetite,
fatigue & desire for sleep, but have high potential for abuse.
They are used in narcolepsy, obstructive sleep apnea (OSA), shift work sleep
disorder (SWSD), attention deficient hyperactivity (ADHD) disorder in children.
They include:
1- Cerebral Cortex Stimulants:
Cerebral Cortex
a- Methyl-xanthines e.g. Caffeine.
b- Cocaine (see Local Anesthetics).
c- Autonomic drugs e.g. Amphetamine, Methylphenidate & Atropine
b- Psychostimulants (Hallucinogenic agents) e.g LSD.
2- Brain Stem Stimulants → Analeptics: as bemegride, doxapram
Stimulate vital centers in brain stem especially RC
3- Spinal Cord Stimulants → Strychnine, antagonist of glycine (Toxic).
Psychotomimetics [Hallucinogens, psychedelics]
Produce symptoms similar to psychosis as hallucinations, elation, delusions.
1- Cannabis (Hashish, Bango, Kif, Marijuana):
1- Active principle is Tetra-hydro-cannabinol → Specific cannabinoid receptors.
2- Cannabinoid receptors are present mainly in CNS & in lymphoid system.
3- Anandamide is an endogenous ligand for the cannabinoid receptors in CNS
2- The person loses the sense of time & space.
3- Euphoria & attacks of uncontrolled laughter.
4- Congestion of conjunctiva,  I.O.P. & Tachycardia.
5- Derivatives used clinically as analgesics & antiemetics e.g. Dronabinol
2- Lysergic Acid Di-Ethylamide (LSD, Acid);
Related to Ergot alkaloids. Central 5-HT Agonist BUT peripheral 5-HT antagonist.
3- Mescaline: Obtained from Mexican cactus. Cross tolerance with LSD.
4- Khat )‫ →(القات‬Amphetamine-like
3- Phencyclidine (PCP , Angle Dust) :
a- Related chemically to Meperidine (Opioid) & Ketamine (IV Anesthesia).
b- It Stimulates -opioid receptor & blocks NMDA-glutamate receptor.
c- Produces Dissociative Anesthesia = Analgesia, stupor & Amnesia. Patient is
conscious but detached from the environment.
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Ali AbdelWahab, Medical Pharmacology & Therapeutics
Methyl-Xanthines
1- Include → Caffeine, Theophylline & Theobromine.
2- Source: Natural Alkaloids of plant origin (coffee, tea, cocoa, cola).
3- They are present naturally in caffeinated beverages:
a- Tea:
Caffeine (30 -50 mg) + Theophylline
b- Coffee: Caffeine (100 – 150 mg)
c- Cola: Caffeine (30 – 50mg)
d- Cocoa: Caffeine (5 – 8 mg) + Theobromine
* Pharmacokinetics:
1- Absorbed orally, rectally (suppository) & parenterally.
2- Distributed all over the body. They pass B.B.B. & placental barriers.
3- Metabolism in liver→ Methyluric acid → Soluble → Not CI in gout.
* Pharmacodynamics:
A) Mechanism of Action of methylxanthines:
Sympathomimetics -Agonists
Methylxanthines
++
-Adenylate
cyclase
Phosphodiesterase
A.T.P.
Active 3’ 5’ cAMP
Inactive 5 AMP
1- Inhibit Phosphodiesterase enzyme IV (PDE-4) →  cAMP.
2- Block adenosine receptors in C.N.S. & periphery.
B) Pharmacological Actions:
Caffeine is Stronger on
→ CNS, skeletal muscles & gastric acidity
Theophylline is Stronger on→ CVS, smooth muscles & kidney
1- C.N.S. Stimulation in a descending manner (Specially Caffeine):
a- Cortex →Mental activity, alertness, Acuity of sensations & Anti-fatigue
Large dose → Insomnia, anxiety & tremors specially in children.
b-  Medulla:  R.C. (Analeptic),  V.M.C.,  Vagal center (C.I.C.).
c-  Spinal cord in large dose.
2- C.V.S.: (Especially Theophylline)
Direct (cAMP) →  Heart →  H.R.,  Contractility,  Work
&  Automaticity
a- Heart
CNS →  C.I.C. →  H.R.
b- B.V.
Direct (CAMP) → VD →  blood pressure
CNS → VMC → VC →  blood pressure
c- Aminophylline Small Dose & Slow IV→ Minimal change in HR & blood pressure
While large dose or rapid I.V. → Direct effect → Tachycardia + Hypotension
d- V.C. of Cerebral arteries
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Ali AbdelWahab, Medical Pharmacology & Therapeutics
3- Respiration:
a- Direct ( cAMP) → Bronchodilatation specially Theophylline
b- C.N.S. →  R.C. specially Caffeine
4- G.I.T.:
a- Caffeine
→  Gastric acidity
b- Theophylline → Spasmolytic & Irritant → Nausea & Vomiting
5- Renal:
a- Theophylline → Spasmolytic action on ureter & bladder
b- Diuretic action: (Theophylline > Theobromine (Longer) > Caffeine)
- Extra-Renal →  C.O.P. + Renal V.D. →  R.B.F. →  G.F.R.
- Renal →  Na & H2O reabsorption from the renal tubules.
6- Smooth Muscles → Spasmolytic specially Theophylline
7- Skeletal Muscles → Stimulation & Anti-fatigue specially Caffeine
Preparations:
-Aminophylline (Theophylline ethylene diamine) ampoules, suppositories
-Theophylline SR tablets, capsules
* Therapeutic Uses Of Methyl-Xanthines:
A) Theophylline:
1- Bronchial Asthma:
- Acute attacks: Aminophylline 250-500 mg Slow I.V. (2-Agonists better)
- Status Asthmaticus: Aminophylline I.V. infusion + steroids + Salbutamol inhalation
- Prophylaxis: # Theophylline S.R. 200 mg / 12 hours
2- Chronic Obstructive Pulmonary Diseases (COPD) e.g. emphysema
3- Cardiac Asthma = Left Ventricular failure = Pulmonary edema:
Aminophylline slowly I.V. (+ve Inotropic, Diuretic & Bronchodilator)
B) Caffeine;
1- With Ergotamine → Cafergot in acute attack of Migraine headache
With Aspirin or paracetamol in simple headache.
2- With Neostigmine in Myasthenia Gravis
3- Fatigue (Physical or mental) & Poisoning by C.N.S. depressants e.g. Hypnotics
C) Pentoxyfylline: methylxanthine derivative used in treatment of:
- Chronic occlusive arterial diseases e.g. intermittent claudication:
It improves RBCs flexibility, fibrinogen, blood viscosity, platelet
aggregation
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Ali AbdelWahab, Medical Pharmacology & Therapeutics
* Adverse Effects of Xanthines:
A) Caffeine:
(Wide safety margin)
1- C.N.S. → Insomnia, anxiety & tremors.
2- G.I.T. → Hyperacidity.
B) Theophylline:
1- Narrow range of therapeutic plasma concentration → 10 – 20 ug /ml.
a- I.M. or S.C. → Painful.
b- Orally → Gastritis (use after meals)
c- Rectally (suppository) → Proctitis specially in children
3- Rapid I.V. injection → Velocity reaction:
a- Heart: -Theophylline → Tachycardia & arrhythmia
-Ethylene diamine → Cardiac arrest
May be FATAL
b- Blood pressure → Severe hypotension & syncope
2- Irritant:
4- C.N.S.: Insomnia, anxiety, tremors & seizures esp. in children
5- C.V.S.: Tachycardia, palpitation, angina, arrhythmia & hypotension
6- G.I.T.: Anorexia, nausea, vomiting & ulceration
C) Long Use:
1- Tolerance & Cross tolerance between the xanthines
2- Psychic dependence for caffeine = Habituation
* Contraindications of Xanthines:
1- Angina (cardiac work), arrhythmia (automaticity) & hypertension (Caffeine)
2- Peptic ulcer
3- Cardiac arrhythmias
* Drug Interactions of Theophylline:
A) Drugs  Metabolism of Theophylline →  its plasma level → Toxicity
a- Cimetidine
b- Antimicrobials: Erythromycin & Quinolones
c- Heart & Hepatic Diseases, and Hypothyroidism
B) Drugs Metabolism of Theophylline →  Its Plasma level →  Effect
a- Rifampicin
b- Anti-Epileptics: Phenobarbitone, Phenytoin & Carbamazepine
c- Hyperthyroidism
d- Tobacco (Heavy smokers) & Alcohol
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Ali AbdelWahab, Medical Pharmacology & Therapeutics
Formative Assessment:
1. Enumerate benzodiazepine agonists, their action, uses and side effects
2. Classify Anxiolytics (sedative & non-sedative)
3. Enumerate therapeutic uses and contraindication of morphine
4. Differentiate between action of morphine and meperidine
5. Enumerate therapeutic uses and adverse effects of Salicylates
6. Enumerate drugs used in treatment of acute attack of gout
7. Mention mechanism of action and adverse effect of Allopurinol
8. Enumerate mechanisms of action of antiepileptic drugs, give examples
9. Explain:
-Addition of carbidopa to I-DOPA
-Fosphenytoin is better than phenytoin in status epilepticus
-Tachycardia and hypotension associated with chlorpromazine
-Aminophylline should not be given by rapid IV
-Addition of adrenaline to local anesthesia
10. Mention adverse effects of carbamazepine, phenytoin & chlorpromazine
11. Compare between I-DOPA and dopamine agonists in treatment of parkinsonism
12. Classify antipsychotic drugs, mention therapeutic uses of chlorpromazine
13. Classify antidepressants, discuss advantages of SSRIs over TCAs
14. Enumerate therapeutic uses and toxicity of TCAs
15. Enumerate inhalation anesthetics, give their specific advantages
16. Compare between Propofol and thiopentone as IV anesthetics
17. Classify local anesthetics and list factors increasing their effect
18. Describe systemic adverse effects of local anesthetics
Review MCQs
1- All of the following are NSAIDs EXCEPT:
a. Ibuprofen
c. Butorphanol
e. Tiaprofenic acid
b. Naproxen
d. Piroxicam
2- Side effects shared by NSAIDs include all the following EXCEPT:
a. Addiction
b. Gastrointestinal ulceration
c. Hypersensitivity
d. Nephropathy
e. Hepatotoxicity
3- Benzodiazepines produce their actions on CNS by:
a. Blocking Cl- channel associated with GABAA receptor
b. Potentiation of the effect of GABA on GABAA receptors
c. Reducing the effect of GABA on GABAA receptors
d. Acting as agonists at GABAB receptors
e. Acting as antagonists at GABAB receptors
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Ali AbdelWahab, Medical Pharmacology & Therapeutics
4- Which of the following drugs acts as a competitive benzodiazepine receptor antagonist:
a. Naloxone
b. Flumazenil
c. Flurazepam
d. Nitrazepam
e. Disulfiram
5- All of the following are naturally occurring opium alkaloids EXCEPT:
a. Morphine
b. Codeine
c. Meperidine
d. Papaverine
e. Narcotine
6- Effects of morphine on CNS include all of the following EXCEPT:
a. Analgesia
b. Miosis
c. Respiratory depression
d. Anticonvulsant effect
e. Depression of cough reflex
7- Effects of morphine on the GIT include all of the following EXCEPT:
a. Increased propulsive peristaltic waves in colon
b. Decreased gastric motility
c. Increased tone of small intestine
d. Decreased biliary, pancreatic and intestinal secretions
e. Increased intrabiliary pressure
8- Which of the following is a pure opioid antagonist:
a. Methadone
b. Nalbuphine
c. Naloxone
d. Buprenorphine
e. Pentazocine
9- The use of morphine is contraindicated in all the following conditions EXCEPT:
a. Head injuries
b. Bronchial asthma
c. Acute left ventricular failure
d. Myxedema
e. Biliary colic
10- Adverse effect of morphine include all of the following EXCEPT:
a. Physical and psychological dependence
b. Constipation
c. Respiratory depression
d. Bronchoconstriction
e. Hyperpyrexia
11- Symptoms of acute morphine toxicity include:
a. Coma, pinpoint pupils and depressed respiration
b. Hyperthermia
c. Abdominal cramps, diarrhea and miosis.
d. Hypertension & cardiac arrhythmias
e. Dry mouth and mydriasis
12- Which of the following drugs is used in treatment of morphine or heroin addiction:
a. Butorphanol
b. Methadone
c. Alfentanil
d. Sufentanyl
e. Dextropropoxyphene
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Ali AbdelWahab, Medical Pharmacology & Therapeutics
13- Which of the following opioid analgesics induces withdrawal syndrome when given t a
morphine addict:
a. Meperidine
b. Methadone
c. Nalbuphine
d. Hydromorphone
e. Fentanyl
14- Pharmacologic actions of acetylsalicylic acid include all of the following EXCEPT:
a. Analgesic
b. Antipyretic
c. Anti-inflammatory
d. Promotion of platelet aggregation
e. Inhibition of synthesis of prostaglandins
15- Aspirin is used in treatment of:
a. Vertigo
c. Acute left ventricular failure
e. Acute rheumatic fever
b. Peptic ulcer
d. Acute bronchial asthma
16- Manifestations of acute salicylate intoxication include all the following EXCEPT:
a. Hyperpyrexia
b. Hyperpnoea
c. Pinpoint pupils
d. Convulsions
e. Metabolic acidosis in children
17- Aspirin could be used prophylactically for which one of the following conditions:
a. Bronchial asthma
b. Angina pectoris
c. Paroxysmal atrial tachycardia
d. Peptic ulcer
e. Hypertension
18- The following has a selective morphine like effect on G.I.T.:
a- Loperamide
b- Pentazocine
c- Heroin
d- Atropine
e- Neostigmine
19- The common mechanism of action of NSAIDs is inhibition of the following enzyme:
a- Cholinesterase
b- Cyclo-oxygenase
c- Lipo-oxygenase
d- Phosphodiesterase
e- Phospholipase
20- The following is a selective COX-2 enzyme inhibitor:
a- Aspirin
b- Indomthacine
c- Diclofenac
d- Celecoxib
e- Paracetamol
21- Aspirin is useful in treatment of:
a- Bronchial asthma
c- Simple headache
e- Viral infection in children
b- Bleeding tendency
d- Peptic ulcer
22- The following are useful in management of an acute attack of gout EXCEPT:
a- Allopurinol
b- Colchicine
c- Indomethacine
d- ACTH
e- Glucocorticoids
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Ali AbdelWahab, Medical Pharmacology & Therapeutics
23- The following drug is used in treatment of benzodiazepine toxicity:
a- Naloxone
b- Flumazenil
c- Diazepam
d- Chlordiazepoxide
e- Triazolam
24- The following anxiolytic acts as a partial agonist on 5-HT1A receptors:
a- Buspirone
b- Flurazepam
c- Diazepam
d- Chloralhydrate
e- Phenobarbitone
25- Trichloroethanol is the active metabolite of:
a- Morphine
c- Phenobarbitone
e- Buspirone
b- Chlorazepate
d- Chloralhydrate
26- The following is a selective serotonin reuptake inhibitor used in treatment of psychic
depression:
a- Imipramine
b- Amitriptyline
c- Fluoxetine
d- Maprotiline
e- Tranycypromine
27- The following drug is useful in treatment of Parkinsonism:
a- L-DOPA
b- Reserpine
c- α-Methyldopa
d- Haloperidol
e- Physostigmine
28- Phenytoin is used in treatment of all of the following EXCEPT:
a- Grand mal epilepsy
b- Petit mal epilepsy
c- Status epilepticus
d- Partial seizures
e- Digitalis induced cardiac arrhythmia
29- Regarding methyl-xanthines, the following statement is WRONG:
a- Caffeine produces CNS stimulation
b- They produce vasodilatation of blood vessels except cerebral
c- They produce spasmolytic effect on bronchi
d- They are contraindicated in gout
e- They are contraindicated in cardiacrhythmias
30- Morphine is useful in treatment of:
a- Acute abdominal pain
c- Bronchial asthma
e- Neurogenic shock
b- Head injury
d- Epilepsy
31- The following is a selective COX-3 enzyme inhibitor:
a- Acetylsalicylic acid
b- Indomethacin
c- Diclofenac
d- Dipyrone
e- Celecoxib
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Ali AbdelWahab, Medical Pharmacology & Therapeutics
32- Acetylsalicylic acid (aspirin) produces all of the following actions EXCEPT:
a- Analgesic antipyretic
b- Anti-inflammatory anti-rheumatic
c- Uricosuric in small dose
d- Anti-platelet in small dose
e- Hydrochloretic
33- The following drugs are useful in management of gout EXCEPT:
a- Thiazide diuretics
b- Colchicine
c- Allopurinol
d- Sulphinpyrazone
e- Benzbromarone
34- The benzodiazepines produce the following actions EXCEPT:
a- Central muscle relaxant
c- Sedative hypnotic
c- Anticonvulsant antiepileptic
d- Anesthesia
e- Hepatic microsomal enzyme induction
35- Slow IV injection of therapeutic dose of aminophylline produces all of the following
actions EXCEPT:
a- Decrease in cardiac output
b- Diuretic effect
c- Stimulation of respiratory center
d- Bronchodilatation
e- Minimal change in blood pressure and heart rate
36- The following receptors are affected by antipsychotic drugs EXCEPT:
a- Central D2-receptors
b- Serotonin 5-HT2 receptors
c- Peripheral H2 receptors
d- Peripheral α-adrenoceptors
e- Peripheral muscarinic receptors
37- The following statements are correct about MAO inhibitors EXCEPT:
a- Their effects persist for more than a week after cessation of administration
b- Combination of old cheese or beer with MAO inhibitors can cause
hypertensive crisis
c- Selegiline (deprenyl ) is a selective MAO (B) inhibitor
d- Combination of a MAO-inhibitor and a selective serotonin reuptake inhibitor
produces a synergistic effect useful in treatment of depression
e- MAO-inhibitors reduce oxidative deamination of noradrenaline, serotonin &
dopamine
38- The following opioid agonist is used in the controlled withdrawal of addicts from
morphine:
a- Meperidine
b- Methadone
c- Propoxyphene
d- Fentanyl
e- Codeine
39- All of the following statements about fluoxetine are correct EXCEPT:
a- It is a selective serotonin reuptake inhibitor
b- It is used in treatment of epilepsy
c- It may cause anxiety and insomnia
d- It has anticholinergic and cardiotoxic effects
e- It may cause sexual dysfunction
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Ali AbdelWahab, Medical Pharmacology & Therapeutics
40- Benzodiazepines have the following actions EXCEPT:
a- They reduce anxiety by inhibiting the neuronal limbic system
b- They produce sedation and hypnosis
c- They have antipsychotic action
d- Several benzodiazepines act as anticonvulsants
e- They cause muscle relaxation
41- A 47-year-old man presents with acute pain in his big toe. Lab tests reveal a serum
uric acid level of 10 mg/dl. After treatment for the acute attack he was shifted to a drug
that decreases both serum and urine level of uric acid. This drug is:
a- Allopurinol
b- Colchicine
c- Indomethacin
d- Probenecid
e- Sulfinpyrazone
42- The following statements about carbidopa are incorrect EXCEPT:
a- It is dopa decarboxylase inhibitor
b- It crosses the blood brain barrier
c- The dose of L-dopa is to be increased when combined to carbidopa
d- Side effects of L-dopa are increased due to carbidopa
e- Carbidopa increases the metabolism of L-dopa in the peripheral tissues
43- The following are true about neuroleptanalgesia EXCEPT:
a- It can be produced by injecting a combination of droperidol and fentanyl
b- It can cause loss of consciousness
c- It has an antiemetic effect
d- It produces good analgesia
e- All of the above
44- Drugs useful to initiate sleep include which of the following:
a- Flurazepan
c- Chlorazepate
e- All of the above
b- Triazolam
d- Phenobarbitone
45- Drug treatment of anxiety states includes the following:
a- Diazepam
c- Alprazolam
e- All of the above
b- Buspirone
d- Propranolol
46- Zolpidem is:
a- Long-acting benzodiazepine
c- Benzodiazepine receptor agonist
e- Potent anti-epileptic
b- Short-acting barbiturate
d- Benzodiazepine antagonist
47- Buspirone is:
a- Sedative drug
c- Has rapid onset of action
e- Liable to addiction.
b- Useful in insomnia
d- Anxiolytic drug
48- Side effects of benzodiazepines include the following except:
a- Tolerance and dependence
b- Convulsions
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Ali AbdelWahab, Medical Pharmacology & Therapeutics
c- Amnesia
e- Allergy
d- Day- time sedation
49- Panic disorders (Phobias) can be treated by:
a- Thiopentone
c- Alprazolam
e- Celecoxib
b- Paraldehyde
d- Chlorpromazine
50- Drugs useful in treatment of schizophrenia include the following except:
a- Thioridazine
c- Clozapine
e- Trifluprazine
b- Theophylline
d- Haloperidol
51- Chlorpromazine produces its antipsychotic effect by:
a- Blocking dopamine receptors
c- Blocking adrenergic receptors
e- All of the above
b- Blocking nicotinic receptors
d- Blocking opiate receptors
52- Anti-psychotic drugs produce the following side effects except:
a- Parkinsonism
c- Hypertension
e- Neuroleptic malignant syndrome
b- Tardive dyskinesia
d- Glactorrhea
53- Psychic depression can be treated by the following:
a- Desipramine
c- Amineptine
e- All of the above
b- Tranylcypromine
d- Fluoxitine
54- Drugs useful in treatment of mania include the following except:
a- Lithium carbonate
c- Carbamazepine
e- All of the above
b- Sodium valproate
d- Diazepam
55- Side effects of MAO inhibitors include the following except:
a- Cheese reaction
c- Hepatotoxicity
e- None of the above
b- Hepatic microsomal enzyme induction
d- Delayed onset of action
56- Antipyretics include the following except:
a- Ibuprofen
c- Acetohexamide
e- Naproxen
b- Acetaminophen
d- Acetylsalicylic acid
57- Severe biliary colic can be treated by:
a- Diclofenac
c- Codiene
e- All of the above
b- Aspirin
d- Acetaminophen
58- Which of the following is useful in treatment of trigeminal neuralgia:
a- Phenylbutazone
c- Atropine
b- Morphine
d- Carbachol
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Ali AbdelWahab, Medical Pharmacology & Therapeutics
e- Carbamazepine
59- Narcotic analgesics include which of the following:
a- Aspirin
c- Codiene
e- Paracetamol
b- Papaverine
d- Indomethacin
60- Celecoxib produces:
a- Inhibition of COX-1 enzyme
c- Inhibition of lipoxygenaze enzyme
e- Diuretic action
b- Inhibition of COX-2 enzyme
d- Antiarrhythmic action
61- All of the following are therapeutic indications for aspirin except:
a- Rheumatoid arthritis
c- Viral infection in children
e- Headache
b- Fevers
d- Unstable angina
62- All of the following can be produced by acetaminophen except:
a- Anti-inflammatory effect
c- Anti-pyretic effect
e- Liver damage on overdose
b- Analgesic effect
d- Inhibition of COX-3 enzyme
63- Which of the following is not a pharmacologic effect of morphine:
a- Analgesia
c- Vomiting
e- Respiratory depression
b- Diarrhea
d- Miosis (PPP)
64- L-Dopa can be used to treat which of the following:
a- Parkinsonism
c- Hypertension
e- All of the above
b- Angina
d- Cardiogenic shock
65- Anti-psychotic drugs include the following except:
a- Haloperidol
b- Fluoxetine
c- Thioridazine
d- Olanzapine
e- Clozapine
66- Anti-convulsant drugs include which of the following:
a- Valproic acid
b- Barbituric acid
c- Mefenamic acid
d- Acetylsalicylic acid
e- Citric acid
67- Drugs useful in anxiety states include the following except:
a- Alprazolam
b- Alprostadil
c- Buspirone
d- Diazepam
e- None of the above
68- Drug of choice in treatment of absence seizures:
a- Ethosuximide
b- Fenoldopam
c- Acetazolamide
d- Carbamazepine
e- Lamotrigine
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Ali AbdelWahab, Medical Pharmacology & Therapeutics
69- Morphine can be used for all the following therapeutic indications except:
a- Pain of myocardial infarction
b- Pain of head injury
c- Post operative abdominal pain
d- Acute pulmonary edema
e- Preanesthetic medication
70- Aspirin has all the following effects except:
a- Antipyretic
c- Analgesic
e- Antiplatlet
b- Anti-inflammatory
d- Antispasmodic
71- The principal use of leflunomide is in the management of:
a- Psoriasis
b- Peptic ulcers
c- Colon cancer
d- Rheumatoid arthritis
e- Acute gout
72- The anti-inflammatory action of aspirin is due to:
a- Analgesic effect
b- Inhibit leukotriens synthesis
c- Inhibit prostaglandin synthesis
d- Effect on hypothamus
e- All of the above
73- All the following agents can be used concurrently with levodopa except:
a- Benztropine
b- Amantadine
c- Carbidopa
d- MAO-A inhibitors
e- Diphenhydramine
74- Excitatory chemical neurotransmitters in CNS include the following except:
a- Serotonin
b- Acetylcholine
c- GABA
d- Noradrenaline
e- Dopamine
75- Which of the following is correct regarding CNS neurotransmitters:
a- Acetyl choline is involved in learning and memory
b- Glutamate and aspartate are involved in postsynaptic inhibition
c- Noradrenaline can potentiate GABA effect
d- Glycine is an excitatory amino acid
e- Dopamine is important in pain neurotransmission
76- Opioid drugs produce the following actions except:
a- Miosis
b- Analgesia
c- Constipation
d- Hypotension
e- Bronchodilation
77- Loperamide is:
a- Analgesic anti-pyretic
c- Anti-diarrheal
e- Anti-convulsant
b- Anti-tussive
d- Anti-emetic
78- Regarding opiate drugs, which of the following is correct:
a- Codeine is an opiate agonist used as antitussive.
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Ali AbdelWahab, Medical Pharmacology & Therapeutics
b- Methadone is used in treatment of opiate overdose.
c- Diphenoxylate is useful in treatment of constipation.
d- Naloxone is a partial agonist at opioid receptors.
e- All of the above
79- Benzodiazepines produce all the following except:
a- Sedation and hypnosis
b- Potentiation of GABA action
c- Skeletal muscle relaxation
d- Epileptic convulsions
e- Taming effect
80- The following drugs are useful as hypnotics except:
a- Lorazepam
b- Zolpidem
c- Paraldehyde
d- Caffeine
e- Phenobarbitone
81- Buspirone produces the following except:
a- Partial agonist at 5-HT receptors
c- Anti-convulsant effect
e- None of the above
b- Anti-anxiety effect
d- Slow onset of action
82- All of the following are useful in Grand-mal epilepsy except:
a- Phenytoin
b- Carbamazepine
c- Lamotrigine
d- Sodium valproate
e- Acetazolamide
83- Phenytoin produces the following except:
a- Hepatic microsomal enzyme inhibition
c- Antiarrhythmic activity
e- Antiepileptic activity
b- Gum hyperplasia
d- Hepatotoxicity
84- Sodium valproate produces the following except:
a- Broad-spectrum anti-epileptic effect
b- Teratogenicity
c- Hepatic microsomal enzyme inhibition
d- Hepatotoxicity
e- Nephrotoxicity
85- Which of the following is a dopa decarboxylase inhibitor:
a- Selegiline
b- Tolcapone
c- L-Dopa
d- Carbidopa
e- Dopamine
86- Treatment of parkinsonism include:
a- Dopamine agonists
c- MAO-B inhibitors
e- All of the above
b- Muscarinic antagonists
d- L-Dopa
87- Bromocriptine can be used in the following except:
a- To supress lactation
b- Parkinsonism
c- Psychosis
d- Galactorrhea
e- None of the above
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Ali AbdelWahab, Medical Pharmacology & Therapeutics
88- L-dopa produces which of the following:
a- Stimulation of dopamine receptors
c- Block 5-HT receptors
e- All of the above
b- Increase dopamine levels
d- Block dopamine reuptake
89- Which of the following is not useful in treatment of parkinsonism:
a- Amantadine
b- Benztropine
c- Selegiline
d- Pramipexol
e- Dopamine
90- Therapeutic uses of chlorpromazine include the following except:
a- Schizophrenia
b- Vomiting
c- Preanesthetic medication
d- Hypotension
e- None of the above
91- Regarding anti-psychotics, which of the following is incorrect:
a- They stimulate D2 receptors
b- Useful in schizophrenia
c- Produce extrapyramidal effects
d- Cause galactorrhea
e- Cause sedation
92- Lithium is:
a- Useful in mania
c- Can produce hypertension
e- None of the above
b- Metabolized by the liver
d- All of the above
93- The following are useful antidepressants except:
a- Amitriptyline
b- Fluoxetine
c- Isoniazid
d- Imipramine
e- Tranylcypromine
94- Tricyclic antidepressants produce the following except:
a- Block dopamine receptors
b- Block serotonin receptors
c- Block muscarinic receptors
d- Block histamine receptors
e- None of the above
95- Tricyclic antidepressants are useful in the following except:
a- Depression and phobias
b- Cardiac arrhythmias
c- Migraine prophylaxis
d- Nocturnal enuresis
e- Obsessive neurosis
96- Side effects of tricyclic antidepressants include the following except:
a- Sedation
b- Cardiac arrhythmias
c- Anti-cholinergic effects
d- Hypertension
e- Cholestatic jaundice
97- Side effects of MAO inhibitors include:
a- Hepatotoxicity
b- Sever hypertension with tyramine
c- Insomnia and tremors
d- All of the above
e- None of the above
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Ali AbdelWahab, Medical Pharmacology & Therapeutics
98- Selective serotonin reuptake inhibitors produce:
a- Anti-depressant action
b- Anti-anxiety action
c- Potent atropine-like action
d- Appetite stimulation
e- Antihypertensive action
99- Paroxetine is:
a- Dopamine agonist
c- Has atropine-like action
e- Antispasmodic drug
b- Antihypertensive drug
d- Selective serotonin reuptake inhibitor
100- Cocaine dependence is characterized by the following except:
a- Insomnia and agitation
b- Hypotension
c- Cardiac ischemia
d- Mydriasis
e- Marked psychic dependence
101- Which of the following drugs has the least anti-inflammatory and ulcerogenic effects?
a- Aspirin.
b- Diclofenac.
c- Ibuprofen.
d- Paracetamol.
e- Indomethacin.
102- Diazepam is useful in management of the following conditions, EXCEPT:
a- Anxiety.
b- Insomnia.
c- Status epilepticus.
c- Skeletal muscle spasticity.
e- Gout.
103- All of the following drugs are considered sedative-hypnotics, EXCEPT:
a- Nitrazepam.
b- Imipramine.
c- Zolpidem.
d- Chloral hydrate.
e- Pentobarbitone.
104- All the following statements are correct except:
a- Alprazolam has antidepressant activity
b- Haloperidol is useful in treatment of psychic depression
c- Lithium excretion is decreased by thiazides
d- Clozapine may cause agranulocytosis
e- Flumazenil is a benzodiazepine antagonist
105- Which of the following pairs of a drug and its indication is FALSE?
a- Thiopentone------Induction of general anesthesia.
b- Isoflurane---------Maintenance of general anesthesia.
c- Procaine----------Production of local anesthesia.
d- Chlorpromazine---Management of hypotension.
e- Imipramine--------Management of nocturnal enuresis.
106- All the following are regarded as antiepileptic (anticonvulsant) drugs, EXCEPT:
a- Phenytoin.
b- Carbamazepine.
c- Levodopa.
d- Sodium valproate.
e- Clonazepam.
107- Which of the following narcotics has the longest duration of effect?
a- Methadone
b- Controlled-release morphine
30
Ali AbdelWahab, Medical Pharmacology & Therapeutics
c- Levorphanol
e- Diydromorphone
d- Transdermal fentanyl
108- Which of the following anticonvulsants is contraindicated in patients with a history of
hypersensitivity to tricyclic antidepressants?
a- Phenytoin
b- Ethosuximide
c- Acetazolmide
d- Carbamazepine
e- Phenobarbital
109- Which of the following mood stabilizers would be most appropriate in a patient with
liver disease?
a- Lithium
b- Valproic acid
c- Carbamazepine
d- All of the above
e- None of the above
110- An advantage of dextromethorphan over codeine as an antitussive is that it:
a- Is twice as effective
b- Is more stable
c- Has no side effects
d- Has better analgesic properties
e- Produces very little depression of the CNS
111- Gold compounds have been used to treat:
a- Hypertension
c- Kidney failure
e- Angina pectoris
b- Peptic ulcers
d- Rheumatoid arthritis
112- Which of the following are NOT correctly paired?
a- Buspirone----- antianxiety agent with negligible addictive liability
b- Alprazolam---- possesses antidepressant activity
c- Baclofen------- less sedation than diazepam
d- Oxazepam----- is a tricyclic antidepressant
e- Imipramine---- not active at GABAA receptors
113- A patient with severe schizophrenia started therapy with clozapine. Which of the
following is the most serious adverse response associated with this drug?
a- Bronchoconstriction
b- Seizures (epilepsy)
c- Serious infection due to agranulocytosis
d- Tardive dyskinesias
e- Profound hypotension due to α-adrenergic blockade
114- Which one of the following drugs causes gum hyperplasia?
a- Chlorpromazine
b- Diphenhydramine
c- Dizaepam
d- Loratadine
e- Phenytoin
115- What group of drugs is known to treat schizophrenia?
a- Antipsychotics
b- Barbiturates
c- SSRIs
d- Phenytoin
e- Older antidepressants (e.g., imipramine)
116- A patient develops status epilepticus. Which of the following drugs or drug
combinations, given IV, is considered “preferred” treatment for this situation?
31
Ali AbdelWahab, Medical Pharmacology & Therapeutics
a- Chlorpromazine followed by haloperidol
c- Flumazenil followed by diazepam
e- Lorazepam followed by phenytoin
b- Valproic acid
d- Haloperidol
117- Both the older (tricyclic) antidepressants and the newer ones (e.g. fluoxetine) relieve
signs and symptoms of depression mainly by doing which one of the following things?
a- Blocking adrenergic and serotonin receptors in the extrapyramidal system
b- Blocking muscarinic receptors in the brain
c- Blocking reuptake of one or more neurotransmitters in the brain
d- Selectively stimulating serotonin receptors
e- Stimulating the synthesis of GABA (gamma-aminobutyric acid)
118- Which one of the following drugs can cause hypotension because it can block alphaadrenergic receptors on vascular smooth muscle cells?
a- Clozapine
b- Diazepam
c- H-1 blockers as diphenhydramine
d- Morphine or other opioids
e- Phenothiazine antipsychotics
119- Which of the following agents is associated with tinnitus as a result of chronic
toxicity?
a- Salicylate
b- Phenytoin
c- Propranolol
d- Acetaminophen
e- Cyclobenzaprine
120- The most serious effect of morphine poisoning is:
a- Renal shutdown
c- Respiratory depression
e- None of the above
b- Paralysis of spinal cord
d- Cardiovascular collapse
121- Salicylic acid is used primarily as a (an):
a- Analgesic
c- Cough suppressant
e- Keratolytic agent
b- Antipyretic
d- Uricosuric agent
122- Which of the following action(s) is produced by lorazepam:
a- Sedation
b- Anticonvulsant action
c- Reduction of anxiety
d- All of the above
e- None of the above
123- Which of the following drugs has been associated with Reye’s syndrome in children?
a- Aspirin
b- Acetaminophen
c- Ibuprofen
d- Naproxen
e- Phenobarbital
124- Probenecid is effective in the treatment of gout because it:
a- Prevents mobilization of leukocytes release of inflammatory mediators.
b- Inhibits xanthine oxidase.
c- Acts to promote excretion of urate (uric acid)
d- Blocks de novo synthesis of urate (uric acid).
e- Inhibits cyclooxygenase (COX) enzyme activity.
32
Ali AbdelWahab, Medical Pharmacology & Therapeutics
125- Potential adverse effects of aspirin include all of the following EXCEPT:
a- Gastrointestinal ulceration
b- Renal dysfunction
c- Reye's syndrome
d- Cardiac arrhythmias
e- Hypersensitivity asthma
126- The following drug is indicated in petit mal epilepsy:
a- Carbamazepine
b- Ethosuximide
c- Phenytoin
d- Phenobarbital
e- All of the above
127- Treatment of acute morphine poisoning includes all the following Except:
a- Gastric lavage
b- Methadone
c- Artificial respiration
d- Purgative with MgSO4
e- Naloxone I.V.
128- Selective serotonin reuptake inhibitors (SSRI) do NOT include:
a- Fluoxetine
b- Paroxetine
c- Sertraline
d- Bupropion
e- Citalopram
129- Which of the following antipsychotic medications has the greatest potential for
extrapyramidal side effects?
a- Haloperidol
b- Clozapine
c- Olanzapine
d- Risperidone
e- Pimozide
130- Selegiline is an antiparkinson agent that inhibits which of the following enzymes in brain?
a- Catechol-O-methyltransferase (COMT) b- Tyrosine hydroxylase (TH)
c- Monoamine oxidase-B (MAO-B)
d- Monoamine oxidase-A (MAO-A)
e- None of the above
131- Tolcapone is an antiparkinson agent that inhibits which of the following enzymes in brain?
a- Catechol-O-methyltransferase (COMT) b- Tyrosine hydroxylase (TH)
c- Monoamine oxidase-B (MAO-B)
d- Monoamine oxidase-A (MAO-A)
e- None of the above
132- Which of the following agents are known to reduce the renal excretion of lithium?
a- Triamterene
b- Thiazides
c- Beta-blockers
d- Alpha-blockers
e- None of the above
133- All of the following are side effects associated with the use of lithium EXCEPT
a- Polydipsia and polyuria
b- Hemolytic anemia.
c- Tremor and confusion.
d- Decreased thyroid function.
e- Edema and weight gain.
134- Which of the following opiate receptors is paired CORRIECTLY with a physiological
or psychological action?
a- Mu receptor--------- dysphoria
33
Ali AbdelWahab, Medical Pharmacology & Therapeutics
bcde-
Kappa receptor------ euphoria
Mu receptor----------- respiratory depression
Delta receptor------- dysphoria
Sigma receptor------ sedation
135- The following opiate drugs are paired correctly with their pharmacological class,
EXCEPT:
a- Heroin----------------- agonist.
b- Dextromethorphan---- mixed agonist/antagonist.
c- Naloxone-------------- antagonist.
d- Butorphanol----------- mixed agonist/antagonist.
e- Fentanyl--------------- agonist.
136- The side effects produced by morphine include which of the following?
a- Stimulation of the cough reflex
b- Diarrhea
c- Dose dependent decrease in respiration
d- Transient hypertension
e- All of the above
137- Halothane produces the following except:
a- General anesthesia with rapid induction
c- Hepatotoxicity
e- None of the above
b- Cardiotoxicity
d- Bronchoconstriction
138- Which of the following is not an intravenous anesthetic:
a- Propofol
b- Propanided
c- Ketamine
d- Nalbuphine
e- Thiopental
139- Halothane general anesthesia has the following advantage:
a- Produces bronchodilatation
b- Adequate muscle relaxation
c- Adequate analgesia
d- Increase uterine response to oxytocics
e- All of the above
140- The following is a local anesthetic amide that has in addition an antiarrhythmic effect:
a- Cocaine
b- Tetracaine
c- Lidocaine
d- Benzocaine
e- Mepivacaine
141- Local anesthetic agents include which of the following:
a- Lidocaine
b- Procaine
c- Bupivacaine
d- Cocaine
e- All of the above
142- Local anesthetic action is related to which of the following?
a- Blockade of voltage-dependent sodium channels
b- Blockade of voltage-dependent calcium channels
c- Frequency of nerve cell firing
d- Resting membrane potential of the nerves
e- All of the above
34
Ali AbdelWahab, Medical Pharmacology & Therapeutics
Indicate which of the following statements is true (T) and which is false (F):
143- Phenobarbitol (Luminol) is a selective GABA receptor agonist. ( )
144- Phenytoin (Dilantin) acts to block inactivated Na channels. ( )
145- Both phenobarbitol and diazepam act on GABAA receptors, with identical mechanisms
of action. ( )
146- Ethosuximide (Zarontin) is a Ca2+ channel inhibitor. ( )
147- Phenobarbital induces P450 enzymes to a greater degree than triazolam. ( )
148- Zolpidem has greater addictive liability than diazepam. ( )
149- Flurazepam has metabolites with much longer half-lives than triazolam. ( )
150- Barbiturates produce more respiratory depression than benzodiazepines in overdose. ( )
151- Ethosuximide is effective in treating both absence (Petit Mal) and tonic-clonic (Grand
Mal) seizures. ( )
152- Acetaminophen is an effective antipyretic, anti-inflammatory, and analgesic agent. ( )
153- Acute acetaminophen overdose may result in hepatic necrosis. ( )
154- Cyclooxygenase-2 enzyme (COX-2) expression is rapidly induced in inflammatory
tissue. ( )
155- Unlike COX-1, COX-2 activity is not inhibited by aspirin and traditional NSAIDS. ( )
156- The overdose of acetylsalicylic acid (aspirin) can be treated with N-Acetylcysteine
(Mucomyst) to inactivate the toxic metabolites. ( )
157- All inhalational anesthetics do not produce loss of pharyngeal reflexes. ( )
158- Inhalational anesthetics that have a high potency also have a low MAC. ( )
159- Induction time of a volatile anesthetic is long if the blood-gas partition coefficient is
high. ( )
160- Diffusion hypoxia can be a problem during recovery with nitrous oxide. ( )
161- Morphine use before anesthesia may increase the amount of thiopental required for
induction. ( )
162- Dizepam not only calms the patient prior to surgery, but also has amnestic actions. ( )
163- Atropine preanesthetic use decreases respiratory secretions and reduces reflex
bradycardia. ( )
164- Propofol is an intravenous general anesthesia. ( )
165- Nitrous oxide is a volatile inflammable liquid used for general anesthesia. ( )
166- Local anesthetics act by blocking Na+ channels. ( )
167- Lidocaine is alocal anesthetic and has anti-arhhythmic action. ( )
168- Amide local anesthetics undergo hydrolysis more readily than esters. ( )
169- Ester local anesthetics are substrates for butyrylcholinesterase. ( )
170- Cocaine is both a local anesthetic and a vasoconstrictor. ( )
171- Epinephrine coadministration with a local anesthetic enhances their systemic
absorption. ( )
35
Ali AbdelWahab, Medical Pharmacology & Therapeutics
Key Answers
Q
A
Q
A
Q
A
Q
A
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
C
A
B
B
C
D
A
C
C
E
A
B
C
D
E
C
B
A
B
D
C
A
B
A
D
C
A
B
D
E
D
C
A
E
A
C
D
B
B
C
A
A
B
B
E
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
61
62
63
64
65
66
67
68
69
70
71
72
73
74
75
76
77
78
79
80
81
82
83
84
85
86
87
88
89
90
C
D
B
C
B
A
C
E
D
B
C
A
E
C
B
C
A
B
A
B
A
B
A
B
D
D
C
D
C
A
A
C
A
D
D
C
E
A
E
D
E
C
B
E
D
91
92
93
94
95
96
97
98
99
100
101
102
103
104
105
106
107
108
109
110
111
112
113
114
115
116
117
118
119
120
121
122
123
124
125
126
127
128
129
130
131
132
133
134
135
A
A
C
A
B
D
D
A
D
B
D
E
B
B
D
C
A
D
A
E
D
D
C
E
A
E
C
E
A
C
E
D
A
C
D
B
B
D
A
C
A
B
B
C
b
136
137
138
139
140
141
142
143
144
145
146
147
148
149
150
151
152
153
154
155
156
157
158
159
160
161
162
163
164
165
166
167
168
169
170
171
C
D
D
A
C
E
A
F
T
F
T
T
F
T
T
F
F
T
T
F
F
F
T
F
T
F
T
T
T
F
T
T
F
T
T
F
36
Ali AbdelWahab, Medical Pharmacology & Therapeutics
OCULAR PHARMACOLOGY
The eye is an organ with multiple autonomic functions, controlled by
several autonomic receptors.
Anatomy and Nerve Supply of the Eye: (Fig.)
* What are the effects of different lesions in the nerve supply to the eye?
Effect of Parasympathetic Stimulation: (M3 R)
1. Contraction of constrictor pupillae muscle (Miosis, wide angle) → ↓ IOP.
2. Contraction of ciliary muscle (cyclospasm, accomodation for near) →↓IOP.
3. Increased lacrimal secretion.
4. Conjunctival vasodilation (congestion).
* Stimulation of Nm R in skeletal muscles causes eye lid twitches.
* Antimuscarinic Drugs; e.g. Atropine and its substitutes; produce passive
mydriasis (↑ IOP, lost light reflex), cycloplegia (↑ IOP, lost accomodation) and
decreased lacrimal secretion.
Effect of Sympathetic Stimulation: (α1 R)
1. Contraction of dilator pupillae muscle (Mydriasis).
2. Contraction of retrobulbar muscle of Muller (Exophthalmos).
3. Contraction of levator palpebrae superioris (Retraction of upper eye lid).
4. Conjunctival vasoconstriction (decongestion).
* Stimulation of β2 R in the ciliary muscle and processes causes ciliary
relaxation and increased secretion of aqueous humour.
37
Ali AbdelWahab, Medical Pharmacology & Therapeutics
DRUGS ACTING ON THE EYE
*MIOTICS:
1- Parasympathomimetics: - Direct: carbachol, pilocarpine
- Indirect: physostigmine, demecarium, echothiophate
(used in glaucoma & hypermetropic accommodative strabismus)
2- Sympatholytics:
guanethidine, phenoxybenzamine
3- Morphine (systemic); st. opiate R in CNS → st. oculomotor nucleus → PPP.
*MYDRIATICS:
1- Sympathomimetics: - Direct: phenylephrine, ephedrine
- Indirect: amphetamine, hydroxyamphetamine
(used in eye congestion, fundus exam. & diagnosis of Horner’s syndrome)
2- Cocaine: surface anesthetic with sympathomimetic activity (↓uptake1& MAOI)
3- Parasympatholytics (Mydriatic cycloplegics): (0.5-2%)
- Natural: atropine, hyoscine (duration 7-10days, used in uveitis & keratitis)
- Synthetic: homatropine (24 h), cyclopentolate (6 h), tropicamide (6 h),
eucatropine (3-4 h, no cycloplegia) (used in fundus exam. & eye adhesions)
4- Ganglion blockers (systemic): produce passive mydriasis & cycloplegia)
*Ocular Routs of Drug Administration:
- Topical administration; solution, ointment, ophthalmic gel, solid insert.
Convenient, safe; but systemic side effects from nasolacrimal absorption
- Subconjunctival injection; for anterior segment infection, but risk of local injury.
- Retrobulbar injection; for post. uveitis & macular edema, but risk of local trauma.
- Intraocular (Intracameral) injection; in ant. segment sergery, but corneal toxicity
- Intravitreal injection; for endophthalmitis & retinitis, but retinal toxicity.
a) Normal Eye
b) Angle-closure Glucoma
b) Open-angle Glucoma
Fig: Secretion and drainage of aqueous
38
Ali AbdelWahab, Medical Pharmacology & Therapeutics
DRUG THERAPY OF GLUCOMA
Glucoma is a major cause of blindness, characterized by increased intraocular
pressure (>30mmHg) with progressive optic nerve damage and visual field loss.
Management includes surgical drainage (iridectomy) or stepped medical therapy to ↑
outflow and/or ↓ secretion of aqueous. Main types include:
- Open-angle (chronic simple) G, treatment mainly medical
- Angle-closure (acute congestive) G, treat. mainly surgical
- Congenital G, treatment mainly surgical
- Secondary G, treatment surgical or medical
- Normal or low-tension G, (? Ocular hypertensives)
A) Cholinomimetics (Miotic eye drops): they ↑ outflow of aqueous, used in all
types of G. (risk of retinal tears & induced myopia)
- Direct agents; pilocarpine (0.5-5%), carbachol (0.5-2%)
- Anticholinesterases;
physostigmine
(0.25-0.5%),
echothiophate (0.03-0.25%) (risk of cataract)
B) Diuretics:
1- Carbonic anhydrase inhibitors: they ↓ secretion of aqueous, used in
open-angle G. (C.I. in kidney stons)
- Systemic CAI; acetazolamide, dichlorphenamid (250mg/8h)
- Topical CAI; dorzolamide, brinzolamide (less side effects)
2- Ethacrynic acid: it ↓ secretion of aqueous, intraocular injection
annually after eye surgery
3- Osmotic agents: they dehydrate the eye, used only in acute attack of
closed-angle glaucoma; mannitol IV, glycerine oral
C) β- adrenergic Blockers: they ↓ secretion of aqueous & may ↑ outflow, used
topically (0.25-0.5%) as first-line in open-angle G. (not affect pupil size or
accommodation, but C.I. in asthma, COPD, bradycardia & HB)
Timolol, betaxolol, carteolol, befunolol, levobunolol, metipranolol
D) α- adrenergic Agonists: used topically in open-angle G.
- Non-selective α- agonists: they ↑ outflow of aqueous &
may↓ secretion; adrenaline (0.1-2%), dipivefrin (0.1%),
phenylepherine (2.5-10%)
- Selective α2- agonists: brimonidine, apraclonidine (0.5-1%);
↓ secretion of aqueous after laser surgery
E) Prostaglandins (topical); latanoprost (prodrug F2α), PGE2, bimatoprost,
travoprost, unoprostone; they ↓secretion and ↑ outflow of aqueous
F) Others; α1- antagonists, marijuana.
N.B.: Drugs C.I. in glaucoma:
- Mydriatic cycloplegics: atropine & its substitutes, TCA, anti-H1, ganglion blockers
- Vasodilators: nitrates & nitrites
39
Ali AbdelWahab, Medical Pharmacology & Therapeutics
DRUGS USED IN TREATING INFLAMMATORY EYE DISEASES
*Topical Anti-infective agents:
- Chloramphenicol 0.5%, used in conjunctivitis, keratitis.
- Tetracycline 1%, used in chronic conjunctivitis, blepharitis.
- Gentamycin 0.3%, used in conjunctivitis, keratitis.
- Ciprofloxacin 0.3%, used in conjunctivitis, keratitis.
- Erythromycin 0.5%, used in conjunctivitis, blepharitis.
- Sulphacetamide 30%, used in trachoma.
- Vidarabine (3%), Acyclovir (3%), used in herpes keratitis.
- Natamycin 5%, Miconazole 1%, used in fungal keratitis.
*Topical Anti-inflammatory and Anti-allergic agents:
- Decongestants; as naphazoline 0.1%, used in conjunctivitis.
- Astringents; as zinc sulphate, used in angular conjunctivitis.
- Anti-histaminics; antazoline, used in allergic conjunctivitis.
- MC stabilizers; cromolyn, ketotifen, used in spring catarrh.
- NSAIDs; diclofenac, ketorolac, used in postop. inflamation.
- Glucocorticoids, used in allergic conjunctivitis, uveitis, optic
neuritis, intraocular inflammations.
- Immunosuppressives; 5-fluorouracil, mitomycin C, used in
eye surgery, serious eye affection in systemic diseases.
*Local anesthetics: - Surface anesthetics; cocaine, tetracaine.
- Infiltration anesthetics; procaine.
*Vitreous Substitutes; as silicone oil, liquid perfluorocarbons & expansile gases;
used in reattachment of retina.
*Diagnostic agents; fluorescein, in diagnosis of corneal ulcers.
DRUG TOXIC EFFECTS ON THE EYE
*Drugs that elevate IOP:
Mydriatic cycloplegics as atropine, topical steroids(in genetically predisposed)
*Drug-induced Cataract:
Systemic steroids (post. subcapsular C.), phenothiazines (ant. polar C.),
organophosphates, heavy metals.
*Drug-induced Retinopathies:
Ethanol, methanol, steroids, indomethacin, ethambutol, chloroquine, quinine,
phenothiazines, chloramphenicol, digitalis.
*Drug-induced Corneal deposits: Amiodarone, chloroquine.
*Oculomucocutaneous syndrome (dryness, opacities, fibrosis); by chronic practolol.
*Retrolental fibroplasias; by prolonged O2 therapy (40%) in premature infants.
*Conjunctival irritation; by ethylmorphine, ether, chloroacetophenone (tear gas).
40
Ali AbdelWahab, Medical Pharmacology & Therapeutics
Review MCQs
1- Drugs that cause dilation of the pupil are:
a. Miotics
c. Cycloplegics
e. Anorectics
b. Mydriatics
d. Antispasmodics
2- The drug producing dilatation of the pupil and lost light reflex could be:
a. Homatropine
b. Ephedrine
c. Cocaine
d. Pilocarpine
e. Physostigmine
3- The following drugs are useful in treatment of glaucoma EXCEPT:
a. Timolol
b. Pilocarpine
c. Atropine
d. Dorzolamide
e. Latanoprost
4- Drugs that facilitate aqueous outflow include:
a. Timolol
c. Acetazolamide
e. None of the above
b. Pilocarpine
d. All of the above
5- Which of the following agents would NOT be appropriate in the treatment of
glaucoma:
a. Pilocarpine
b. Physostigmine
c. Tropicamide
d. Timolol
e. Adrenaline
6- Which of the following drugs can cause miosis and eye lid twitches
a. Pilocarpine
b. Adrenaline
c. Bethanechol
d. Timolol
e. Physostigmine
7- Which one of the following drugs reduces the production of aqueous:
a. Beta-blockers
b. Miotics
c. Prostaglandin analogues
d. Hyperosmotic agents
e. All of the above
8- Which of the following drugs can cause passive mydriasis:
a. Cocaine
b. Ephedrine
c. Atropine
d. Adrenaline
e. Guanethidine
9- Miosis is one of the diagnostic signs in toxicity of the following drug
a. Ephedrine
b. Amphetamine
c. Metriphonate
d. Propranolol
e. Phenoxybenzamine
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Ali AbdelWahab, Medical Pharmacology & Therapeutics
Key Answers
Q
A
1
2
3
4
5
6
7
8
9
B
A
C
B
C
E
A
C
C
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