1- Xanthine

Mechanism of action:
1) Inhibition of phosphodiesterase type 4, so increase c-AMP
2) Blockade of adenosine receptors

Uses:
1) Bronchial asthma (prophylaxis, acute attack and status asthmaticus.
2) Cardiac asthma = paroxysmal nocturnal dyspnea
3) Biliary, renal or intestinal colic.
4) Caffeine in simple headache (combined with paracetamol or aspirin)
and in migraine (caffeine + ergotamine).
5) Caffeine or theophylline in apnea of preterm infants.
6) Caffeine to antagonize cortex depression
7) Pentoxyphylline in intermittent claudication.

Toxicity:
1) Insomnia, restlessness, excitement, and delirium.
2) Tachycardia, extrasystole.
3) Large doses or rapid I.V. administration produces headache, palpitation, dizziness,
nausea, vomiting, tachycardia, hypotension, and sudden death due to arrhythmia.
4) High plasma concentration may lead to convulsions (seizures).
5) Habituation on prolonged use and some tolerance occurs.

Precaution during IV injection :

‫مش موجودة ف الكتاب وكدا كدا مش هتيجي‬

2- Benzodiazepine
Mechanism of action:
Benzodiazepines act on specific receptors so enhance the effect of GABA on GABAA
receptors without directly activating GABA receptors or opening the associated Cl- channel
but increase the frequency of channel opening leading to Cl- influx → Hyperpolarization →
Post-Synaptic Inhibition of neurons

Therapeutic uses:
1- Treatment of anxiety.
2- Sedative and hypnotic in insomnia.
3- Muscle spasm and rigidity.
4- Status epilepticus (by diazepam or lorazepam) and petit mal epilepsy (by
clonazepam).
5- Preanesthetic medication: e.g. Diazepam & Midazolam
6- Treatment of alcohol withdrawal.
7- Alprazolam is used in anxiety with depression and panic disorder.
Advantages over barbiturates
• High therapeutic index (wide safety margin).
 • Minimal effect on sleep rhythm (Little or no hangover).
• Mild physical dependence.
• Little respiratory depression and little cardiovascular effects.
• Not significantly enzyme inducers (so little interactions).
• Slow development of tolerance.
• Available specific antidote= Flumazenil.
Adverse effects:
1- Confusion, anterograde amnesia, dysarthria, weakness, and headache
2- Hypotension and syncope particularly in elderly.
3- Ataxia, increased reaction time, nightmares, hallucination, euphoria
4- Depression, impair mental, psychomotor, and sexual function.
5- Nausea, vomiting, epigastric distress, diarrhea, dry mouth, bitter taste.
6- Bone marrow depression.
7- Thrombophlebitis after I.V. administration.
3- Porphyria
‫ولله ما هتجي ف االمتحان بلص انا مش القيها أصل ف الكتاب‬

4- Melatonin agonist
Action and uses hypnotic to induce sleep.
Advantages: minimal rebound insomnia or abuse liability.
5- Antianxiety ( buspirone )
Mechanism of action:
• Acts as a partial agonist on 5-HT1A presynaptic receptors in brain.
Uses:
• Effective in generalized anxiety syndrome when delayed onset is accepted.
Side effects:
• Tachycardia, palpitation.
• hypertension with MAOIs
• Nervousness, paraesthesia.
• gut upset, miosis Psychomotor impairment is less than benzodiazepines
6- Inhalation anesthesia
1- Halothane :
Advantages:
• Non-inflammable, non-explosive, and non irritant.
• Produces bronchodilatation.
• Produces controlled hypotension.
Disadvantages:
• Inadequate muscle relaxation.
• Poor analgesic.
• Uterine relaxation and reduced response to oxytocic drugs.
 • Bradycardia and sensitization of heart to catecholamines producing cardiac
arrhythmias.
• Induces malignant hyperthermia.
• Expensive.
• Delayed hepatic toxicity.
2- Enflurane
Advantages:
• Non-inflammable.
• Good muscle relaxation.
• Bronchodilator
Disadvantages:
• Relax uterus.
• Sensitizes heart to catecholamines (less than halothane).
3- Nitrous oxide

Advantages:
• Non-inflammable and non-explosive.
• Non-irritant.
• Rapid induction and recovery.
• Good analgesic in labor.
• No effect on respiration or C.V.S. if hypoxia is avoided.
Disadvantages:
• Not potent anesthetic.
• Inadequate muscle relaxation.
• Diffusion hypoxia (during recovery if diffuses rapidly outwards and so lower O2
concentration in alveolar air → hypoxia, so give O2 during recovery.
7- I.V Anesthesia
1- Benzodiazepines

Diazepam, Lorazepam and Midazolam are the members useful clinically as IV anesthetics
• When used with opioids, cardiovascular and respiratory depression may be
severe
• Preoperatively for sedation and reduce anxiety.
• as anesthetic agents for surgical and diagnostic procedures e.g., endoscopy and
cardiac catheterization.
• Produce anterograde amnesia (amnesia for the events that occur after the drug is
administered)
 2- Propofol

• Has rapid onset, short duration and produces hypnosis

• Faster than thiopental
• Used for the induction and maintenance of anesthesia
• No analgesia
• Produces minimal postoperative nausea and vomiting.
• Produces pain at injection site
3- Ketamine

• Act on N-methyl-D aspartate (NMDA)-receptors to block the effects of glutamic acid.

• Has analgesic effect
• Has an amnestic action
• A potent bronchodilator. So, it is useful in asthmatics
• Used for minor procedures especially in infants and children
• Increases blood pressure, heart rate and cardiac output due to sympathetic
stimulation.
• Increases intracranial pressure. So, contraindicated for patients with brain tumors and
head injuries.
• Increase IOP. So contraindicated in glaucoma
• Ketamine produces Dissociative anesthesia (loss of motor activity + analgesia +
amnesia without actual loss of consciousness) in which patients feel dissociated from
their surroundings
• Dreams and terrifying hallucination during recovery occur (emergence phenomenon
which can be controlled by diazepam)
4- Thiopentone
Benzodiazepines
• Thiopental sodium 2.5% solution not more than 1gm.
• It is highly lipid soluble, concentrated in C.N.S. then redistributed, their metabolism is
relatively slow.
Actions:
A. C.N.S :
• Rapid hypnosis with loss of consciousness (~ 20 seconds) leading to surgical
anesthesia, with short duration (5-10 minutes) due to redistribution
• No analgesic action but potentiate analgesics.
• Anticonvulsant action.
B. Respiration: may produce laryngospasm or bronchospasm and  R.C.
C. C.V.S: Large dose rapidly → hypotension.
No sensitization to catecholamines.
Uses:
• Induction of anesthesia.
• General anesthesia for short operations.
• Anticonvulsant in status epilepticus.
Adverse effects:
• Apnea, laryngo- or bronchospasm.
• Thrombophlebitis at site of injection.
• Hypotension in hemorrhagic shock and in elderly.
• Pain, V.C., thrombosis and necrosis if given intra-arterial.
8- Antiepileptic drugs
lamotrigine is antiepileptic drug used in pregnancy
1- Phenytoin

Mechanism of action

• Sodium channel blocker in brain

Uses:
• Grand mal and partial seizures (not in petit mal).
• Treatment of arrhythmia especially induced by digitalis.
Adverse effects:
1. Gingival hyperplasia, hirsutism, Ostomalacia (alter Vit. D metabolism and inhibit
Ca++ absorption).
2. Gastrointestinal irritation (so given with meals), hepatitis.
3. Ataxia, diplopia, vertigo, nystagmus.
4. Blood dyscrasias, hypersensitivity reaction.
5. Teratogenic effects.
6. Megaloblastic anemia (due to decreased folic acid absorption).
7. Inhibit ADH and insulin secretion, increase metabolism of vitamin K.

2- Phenobarbitone

Mechanism of action
• Potentate effect of GABA

Uses:
• Grand mal and partial seizures, but worsen petimal seizure - Status epilepticus (slow I.V)
but not 1st choice

Adverse effects:
1) CNS: Ataxia, diplopia, vertigo, nystagmus
2) Liver : hepatic microsomal enzyme inducer
3) Blood : Megaloblastic anemia / Ostomalacia.
4) Teratogenic effects
5) Tolerance & dependence 6. Respiratory depression

3- Carbamazepine
Mechanism of action:
• Blocks Na+ channels as phenytoin.
Uses:
• Effective in grand mal epilepsy
 • Simple and complex partial seizures in trigeminal neuralgia
• Diabetes insipidus.
Adverse effects:
Nausea, vomiting, diarrhea, dizziness, ataxia, diplopia, antidiuretic effects, skin rashes, hepatitis,
and bone marrow depression.

4- Ethosuximide
Carbamazepine
Mechanism of action:
• blocks Ca++, channels T-type
Uses:
Petit mal epilepsy (drug of choice).
Side effects:
• Gastrointestinal intolerance
• Drowsiness, mood changes,
• Blood dyscrasias
• Allergy.
5- Valproic acid

Mechanism of action:
• Acts by increasing level of GABA by inhibiting GABA transaminase that is
responsible for breakdown of GABA.
• It also blocks Na+ and Ca++ channels.
Uses:
Effective in all types of epilepsy.
Adverse effects:
Sedation, ataxia, nausea, gastric irritation, thrombocytopenia, drug hepatitis, transient hair
loss and teratogenic effect (may produce spina bifida).

6- Trimethadione (Paramethadione)
Uses:
Petit mal epilepsy
Adverse effects:
Sedation, hemeralopia or glare effect (blurred vision in bright light), nephrotic syndrome,
exacerbate grand mal epilepsy, hepatitis, and bone marrow depression.
9- Antiparkinsonism types value of dopa decarboxylase inhibitor
Value
Since more than 95% of administered dose is converted into dopamine in peripheral tissue
and so only small amount enters C.N.S. Therefore, L-dopa is combined with peripheral
decarboxylase inhibitor that cannot pass to brain and thus increases brain level of
dopamine and central adverse effects but decreases peripheral one.
L-dopa (250 mg) + carbidopa (25 mg) → Sinemet.
L-dopa (100 mg) + benserazide (25 mg) → Madopar
Types
A) Dopaminergic Drugs
B) Drugs blocking cholinergic receptors
10- Antipsychotic (chlorpromazine)
Mechanism of action:
• blocking dopaminergic receptors in limbic system (D2).
Adverse effects:
1. Cholestatic jaundice (allergic intrahepatic obstruction).
2. Acute dystonia.
3. Parkinsonism.
4. Akathisia (motor restlessness) and perioral tremors.
5. Postural hypotension.
6. Tardive dyskinesia (oral-facial dyskinesia) on long use.
7. Allergic reaction: blood dyscrasias, dermatitis, corneal and skin deposits, and
photosensitivity.
8. Weight gain.
9. Amenorrhea, galactorrhea, prolactin, infertility, loss of libido and impotence.
11- Antidepressants
1- MAO Inhibitor

Actions:
1- Elevation of mood by increasing the level of 5-HT and catecholamines in brain.
The effect appears after few weeks.
2- Some of them release noradrenaline as tranylcypromine.
Uses:
1- Psychogenic depression.
2- MAO-B inhibitor in parkinsonism.
Adverse and toxic effects:
1- Tremors, insomnia, confusion, convulsions, fatigue,
2- Sweating (hyperhidrosis), difficulty of micturition, constipation, dry mouth inhibition of
ejaculation,
3- Postural hypotension.
4- Hepatocellular damage (with hydrazine group)
5- Optic nerve damage and peripheral neuritis.
6- Hypertensive crisis if patient eats food-containing tyramine.

2- Tricyclic antidepressants

Include:
A) First generation tricyclic antidepressant:
• Imipramine and its major metabolite desipramine.
• Amitriptyline and its metabolite nortriptyline.
Mechanism of action:
By cocaine like action, they prevent uptake I of noradrenaline, and serotonin.
Uses:
1. Depression and panic anxiety disorders and obsessive-compulsive
disorders.
2. Nocturnal enuresis.
3. Chronic pain, neuralgia, and migraine headache.
Side effects:
1. Blurred vision, dry mouth, tachycardia, palpitation, urine retention, constipation,
postural hypotension, and weight gain.
2. Sweating, tremors, confusion.
3. Skin rashes and cholestatic jaundice.
4. Overdose produces cardiac toxicity, convulsion and coma

3- Selective serotonin reuptake inhibitor ( Fluoxetine )

Therapeutic Uses:
1. Psychic depression
2. panic disorders
3. Obsessive-compulsive disorders (better than the TCA clomipramine).
4. Eating disorders e.g., Bulimia nervosa.
Adverse Effects of Fluoxetine:
1. Anorexia, nausea & diarrhea.
2. Anxiety, insomnia & mania.
3. Increases aggression, violence & suicide.
4. Fluoxetine + MAOI → Serotonin syndrome. May be FATAL.

12- Lithium carbonate

Mechanism of Action:
 Frequency & severity of mania by  release of noradrenaline, serotonin & dopamine.
Therapeutic Uses: mood stabilizer for:
1- Prophylaxis of Manic-Depressive disorder.
2- Prophylaxis of recurrent endogenous depression.
3- Acute mania but slow onset. So, add antipsychotic drug as haloperidol
4- Management of aggressive & violent behavior in prisoners.
Adverse Effects :
1- C. N. S : Tremors, dyskinesia & Confusion.
2- Thyroid: Hypothyroidism, benign enlargement of thyroid gland (Goiter).
3- C. V. S : Depresses S A node.
4- Renal :
• Initial polydipsia and polyuria.
• Nephrotoxic
5- Edema: Na+ and water retention, may be via increased release of aldosterone
6- Weight gain
7- During Pregnancy & Lactation:
A. Teratogenic
B. Lithium is secreted in milk & affects suckling baby causing lethargy.
8- Skin: Acneiform eruptions characterized by papules and pustules and folliculitis.
9- Leukocytosis
10- Diminished sexual functions