pharms Flashcards
Mechanism of Action of benzodiazepines:
Bz stimulate specific Bz-receptors — Facilitate GABAA transmission —
Increases CI-influx — Hyperpolarization — Post-Synaptic Inhibition of neurons.
pharmacological actions of benzodiazepines
1- Anxiolytic (Anti-Anxiety):
2- Hypnotic Effects:
long acting benzodiazepines that have anxiolytic action
Diazepam, Chlordiazepoxide and Clorazepate.
intermediate acting benzodiazepines that have anxiolytic action
Oxazepam, Lorazepam and Alprazolam.
Midazolam!
short acting benzodiazepines
Triazolam!
short acting benzodiazepines
Alprazolam!
intermediate acting benzodiazepines
Clonazepam!
intermediate acting benzodiazepines
Estazolam!
intermediate acting benzodiazepines
Lorazepam!
intermediate acting benzodiazepines
Oxazepam!
intermediate acting benzodiazepines
Temazepam!
intermediate acting benzodiazepines
Chlordiazepoxide!
long acting benzodiazepine
Clorazepate
long acting benzodiazepine
Diazepam
long acting benzodiazepine
Flurazepam
long acting benzodiazepine
Prazepam
long acting benzodiazepine
Quazepam
long acting benzodiazepine
long acting benzodiazepines that have hypnotic effect
Flurazepam & Nitrazepam
Intermediate Acting benzodiazepines that have hypnotic effect
Temazepam
short Acting benzodiazepines that have hypnotic effect
Triazolam
IV Anesthesia benzodiazepine
Diazepam
Midazolam
benzodiazepine that has antidepressant effect
Alprazolam
Therapeutic Uses of benzodiazepines
1- Anxiety.
2- Insomnia:
a- Initiate sleep by Triazolam.
b- Maintain sleep by Temazepam or Flurazepam.
3-Preanesthetic medication
4- I.V. Anesthesia
5. Antispasticity
6. Anticonvulsant & Anti-Epileptic:
Adverse Effects of benzodiazepines
1- Dependence — Addiction. Sudden withdrawal — Anxiety & convulsions.
2- Daytime sedation after long acting Bz or Anxiety after short acting Bz.
3- Affect mental. Psycho-motor & Sexual functions.
4- Amnesia (especially Triazolam).
5- Aged patients — mental confusion & hypotension.
6- Additive to Alcohol — Severe CNS Depression.
7- Ataxia.
8-Amenorrhea, decreased Ovulation, decreased Ejaculation & Teratogenic.
9- Increases Appetite — increased Body weight.
10- Allergy.
11-Acute toxicity: Rare unless if used with alcohol — Inhibition of CNS, CVS &
Respiration.
Treatment of Toxicity of benzodiazepine
Flumazenil
Bz1 receptor agonists
Zolpidem, Zaleplon, Zopiclone
Actions of Barbiturates on C.N.S:
1- Sedative action BUT-> Drowsiness.
2- Hypnotic action BUT Abnormal sleep - inhibition of REM:
3- Amnesia.
4- General anesthesia, especially Ultra-short acting barbiturates as Thiopentone.
5- Anticonvulsant as Phenobarbitone
Anti-Epileptic (Phenobarbitone treats Grand Mal & worsens Petit mal epilepsy).
Mechanism of Action of Barbiturates:
Stimulate Specific Barbiturate receptor > GABA-mimetic & facilitate GABA-A transmission - increase CI- influx - Hyperpolarization - Post- synaptic inhibition.
I.V. Anesthesia barbiturates
Thiopentone
barbiturate treats Grand mal epilepsy, Status epilepticus, febrile convulsions.
Phenobarbitone
Adverse Effects of Barbiturates:
Acute Porphyria
Excitation.
Induction of H.M.E. - Tolerance, Cross tolerance, Dependence & Drug Interactions.
Allergy.
Abnormal Sleep - inhibition of R.E.M. - Hang-over & Rebound insomnia.
Amnesia &Automatism.
Acute Poisoning:
Hypnotic, can be used in extremities of age, especially in children
Chloral Hydrate
Melatonin Agonists:
Melatonin, Ramelteon,
Tasimelteon
Orexin receptor Antagonist:
Suvorexant
Mo
MoA of suvorexant
Suvorexant block these OX 1 & 2 receptors to reduce wakefulness and enhance normal sleep.
(orexin is a central peptide neurotransmitter that regulate diurnal rhythm. it high in daylight and low in night to contro wakefullness)
drug block OX 1 & 2 receptors
suvorexant
Anti-depressant used as anxiolytics
Selective serotonin reuptake inhibitors or
Serotonin/norepinephrine reuptake inhibitors (SNRIs)
drug that its actions are mediated by: serotonin (5-HT14) receptors (a partial agonist), with some affinity for D2 dopamine receptors and 5-HT2a serotonin receptors.
buspiron
buspiron used as
anxiolytic
Treats BOTH Psychic & Somatic (Sympathetic) components of anxiety.
Propranolol
typical anti-psychotic drugs
1- Phenothiazines
2- Thioxanthenes
3- butyrophenones
major drug of Phenothiazines
Chlorpromazine
azines
Pharmacodynamics of phenothiazines on CNS
a- Antipsychotic — Blocks Dopamine (D2-receptor)
b- Basal Ganglia — Block D2-receptors — Worsen Parkinsonism.
¢- Hypothalamus:
Hypothermia - Heat loss by cutaneous VD (8 HRC, & VMC &a-Blocker)
increase Appetite & Weight gain.
increase Prolactin.
d- decrease C.T.Z.: Antiemetic in ALL vomiting EXCEPT in motion sickness.
Pharmacodynamics of phenothiazines on Endocrine
a- decrease ACTH
b- decrease FSH &% LH gonadotrophins — Infertility & Amenorrhea in females.
¢- increase Prolactin — Gynecomastia & Galactorrhea
effect of phenothiazines on receptors
potent anti dopamine
potent a blocker
potent antiserotonin
weak anti muscarinic
weak ganglion blocker
weak h1 blocker
therapeutic uses of phenothiazines
1- Psychosis
2- preanesthetic
3- hypothermic
4 hiccough
5- anti-emetic
tadverse effect of chloropromazine
sedation
Acute dystonia
Akathisia
parkinsonism
Neurolept-malignant syndrome (NMS).
Tardive dyskinesia after long use of neuroleptics
causes Neurolept-malignant syndrome
Chlorpromazine
Pharmacodynamics of phenothiazines on CVS
- Hypotension & Postural Hypotension —decrease VMC due to a blocker»_space;> direct VD
- Tachycardia
treat Neurolept-malignant syndrome causd by Chlorpromazine
IV diazepam or IV dantrolene
Drug Interactions of Chlorpromazine
1- Chlorpromazine Potentiates
a- Sedatives e.g. Alcohol.
b- Hypotensive e.g. V.D. and alpha blockers
¢- Anti-cholinergic e.g. Atropine
d- Muscle relaxants e.g. Curare
2- Chlorpromazine —a-blocker — Reverses pressor effect of Adrenaline.
Phenothiazine, more potent than chlorpromazine and why?
Trifluperazine
more POWERFUL Anti-psychotic &More Extrapyramidal manifestations.
the Butyrophenones
Haloperidol & Droperidol
used as depot preparation for maintenance treatment in case of non-compliance
Haloperidol decanoate
used in IV. Neurolept Analgesia
Droperidol + Fentanyl (Opioid Analgesic)
treat Neurolept malignant syndrome by
IV diazepam or IV dantrolene
Atypical Anti-Psychotic Drugs that has high incidence of agranulocytosis
clozapine
fluoxetine
Selective serotonin re-uptake inhibitors (SSRI)
imipramine
Tricyclic anti-depressants
venlafaxine
Selective norepinephrine serotonin reuptake inhibitors
trazodone
Serotonin (5-HT) receptor modulators
bupropion
unicyclic antidepressants
Pharmacodynamics of Fluoxetine
Antidepressant Effect appears after 2-3 WEEKS and lasts for 2-3 WEEKS after stop of SSRI
Therapeutic Uses of fluoxetine
Psychic depression
panic disorders
**Obsessive compulsive disorders **
Eating disorders {Bulimia nervosa} » Ineffective in anorexia nervosa
Post-traumatic stress disorder
Premenstrual syndrome — for 2 weeks in Iuteal phase
Premature ejaculation
how to be caution in giving fluoxetine with MAOIs
Stop fluoxetine 4-5 weeks before initiating MAOIs
Mechanism of Action of TCA:
Inhibit Neuronal Uptakes of Noradrenaline & Serotonin—1 NA, 5-HT Inter-Synaptic.
Actions of Tricyclic Antidepressants
1- Antidepressant Effect:
2- SEDATION:
3- Lower Seizure Threshold.
4- Anti-Cholinergic (Anti-Muscarinic = Atropine-Like).
Amitriptyline > Imipramine > Desipramine.
5- Anti-Histaminic (H1-Block) &Ha-Block.
6- Anti-Serotonin.
7- Alpha blocking effect.
members of TCA
1-Imipramine
2-Desipramine
3-Clomipramine
4-Amitriptyline
5- Nortriptyline
anti depressant used in nocturnal enuresis
Imipramine
treat toxicity of imipramine
ICU - Stomach wash + Charcoal.
+ Diazepam — Treats excitement & Seizures.
+ Phenytoin — Treats Seizures & Ventricular arrhythmias.
+ Physostigmine — treats Atropine-like effects.
Inhibits reuptake and stimulates release of NA
Bupropion
drug interaction of nefazodone
Inhibit metabolism of triazolam and simvastatin
from SNRI doesn’t have adverse effect on CNS
Milnacipran
Therapeutic Uses of bupropion
1- Psychic depression
2-Reduced craving to smoking— As effective as nicotine patches. WHY?
- Mimics effects of nicotine over NA
- Non-competitive blocker of nicotine receptors
- Substitutes for antidepressant effect of nicotine
3-Obesity
4-SSRis-associated sexual side effects
mood stabilizing drugs (antimanic)
1- Lithium carbonate
2- Sodium valproate
3- Carbamazepine (oxcarbazepine is ineffective)
4- Lamotrigine
antidepressant used in ceasing smoking
bupropion
Herbal Antidepressants:
St. John’s Wort
urinary excretion of lithium is increased by
Na load
alkalinizer of urine
osmotic diuretics
acetazolamide
loop diuretics
urinary excretion of lithium is increased by
hyponatriemia
thiazide diuretics
Spironolactone
Mechanism of Action of lithium carbonate
decrease release of noreadrenaline, serotonin & dopamine
Adverse Effects & Toxicity of lithium carbonate
- Thyroid: Hypothyroidism, Smooth benign enlargement of thyroid gland (Goiter)
- a- Initial polydipsia and polyuria » Uncoupling of vasopressin from G proteins»_space; nephrogenic diabetes insipidus.
- Teratogenic P Ebstein’s anomaly
- overdose needs hemodialysis
Therapeutic Uses of lithium carbonate (mood stabilizer)
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.
treatment of toxicity of lithium carbonate on kidneys and ADH disorder
amiloride
how to deal with over dose of lithium carbonate
Hemodialysis
Anti-Parkinsonian Drugs
Dopaminergic Drugs
1- Levodopa(L-DOPA) + peripheral dopa decarboxyalse inhibitors Carbidopa
2- COMT-Inhibitors: Tolcapone & Entacapone.
3- MAO-B Inhibitors: Selegiline.
4- Direct Dopamine Agonists: bromocriptine
Anti-Cholinergic Drugs
Benztropine.
Benzhexol
Biperiden
COMT inhibitors
Tolcapone
Entacapone
Opicapone
what is mao b inhbitors
inhibit enzymers mao b that metabolize dopamine
Bromocriptine used in
a- Parkinsonism — Monotherapy or as Add-on to Sinemet.
b- Prolactin — Treat Hyperprolactinemia e.g. Galactorrhea-amenorrhea syndrome.
¢- Suppress lactation. Safer than Estrogen.
d- Acromegaly.
antiviral agent and treats parkinsonism
Amantadine
used as an adjunct treatment to L-DOPA and carbidopa to treat the “off” episodes.
Istradefylline
Used mainly to treat latrogenic Parkinsonism induced by neuroleptic drugs.
Anticholinergic drugs : benzotropine, benzhexol, biperiden
common antiepleptic drug
phenytoin
uses of phenytoin
- Grand Mal Epilepsy & Partial seizures (No Sedation).
2- Status Epilepticus (not first-line).
3-Class-1 Group-B Anti-Arrhythmic Useful in treatment of Ventricular arrhythmia with Heart Block— Drug of Choice in Digitalis-Induced arrhythmia.
causes ginvial hyperplasia
phenytoin
carbamzepine uses
Grand Mal Epilepsy & Partial seizures
Trigeminal neuralgia
Mood stabilizer
Drug of choice in patients with:
- Mixed Petit mal + Grand mal epilepsy.
- Myoclonic epilepsy.
Valproic Acid or Sodium Valproate
First choice:
Absence Seizures = Petit Mal Epilepsy:
Ethosuximide
first-line drug of choice for generalized absence seizures (Petit Mal
epilepsy)
Ethosuximide
First choice:
Grand Mal Epilepsy & B) Partial seizures:
Carbamazepine & lamotrigine & phenytoin
First choice:
Mixed Petit mal + Grand mal epilepsy:
Valproate
First choice:
Status Epilepticus treatment:
diazepam or lorazepam
phenytoin
fosphenytoin
phenobarbitone
First choice:
Drug-induced Seizures:
Benzodiazepines
First choice:
Febrile convulsions in children
Valproate,
absorption of morphine
SC and IM
in shock»_space; slow diluted IV
what morphine causes to baby during labor
Neonatal asphyxia
How to treat Neonatal asphyxia
Treat by Naloxone
more active than morphine
morphine 6 glucuronide
treat toxicity of morphine
stomach wash
w
mechanism of action of morphine
1- Inhibit Adenylate cyclase — Decrease CAMP
2- Open K* Channel — Hyperpolarization.
3- Block Ca Channel — Decrease Release of transmitters
effect of morphine on CNS
depressant actions:
analgesic of pain
narcosis
cough center
VMC
HRC
hormones ACTH FSH & LH
stimulant actions:
1) euphoria
2) 3 cranial nerve miosis
3) vagal center bradycardia
4)
وجع سناتر هرموات رفلكسات
causes Pin Point Pupil
morphine
Morphine-like on GIT —Treat diarrhea with
minimal or No CNS actions.
Loperamide & Diphenoxylate
mechanism of action of morphine
Effective in all types of pain especially Deep visceral pain.
Inhibits Release of Substance-P & Glutamate in Substantia gelatenosa
inhibit pain transmission
A.N.S inhibit sympathetic and induce parasympathetic
Eye»_space; Miosis»_space; Pin Point Pupil (PPP)
C.V.S.—»Bradycardia & Hypotension
respiratory (Depresses R.C.- depresses cough center- Histamine release» bronchospasm)
spasmogenic
1) smooth muscle
2) GIT»_space; constipation
3) biliary tract
4) urinary tract
Specific Morphine Antagonists
Naloxone
Adverse Effects of Morphine
1- Interfere with proper diagnosis of Head injury & Acute abdomen.
2- Inhibition of Respiration
3- Pin point pupil (PPP)
4- Nausea & Vomiting
5- Bronchospasm
6- Constipation
7- Retention of urine
8- Neonatal asphyxia
9- ltching
10- Tolerance & cross-tolerance with other Opioids.
imp morphine adverse effects
Acute Morphine Poisoning:
Chronic Poisoning» Addiction
Therapeutic Uses of Morphine
1- Pain: Analgesic in Severe Visceral Pain
2- Pulmonary Edema due to Acute Left Ventricular Failure
3- Primary Neurogenic shock
4- Preanesthetic medication:
to treat renal and biliary colic by morphine you should add
artopine
management of Morphine addiction
- Hospitalization + Psychotherapy.
- Gradual withdrawal of Morphine till the stabilizing dose.
- Gradual substitution with Methadone— Similar to Morphine put Less withdrawal manifestations
- Gradual withdrawal of Methadone.
- Clonidine — Control many withdrawal symptoms.
- Acupuncture — Increases Release of endogenous endorphins & enkephalins.
- Oral Naltrexone —p-Antagonist — inhibits Euphoria — Dysphoria.
Contraindications of Morphine
Head injury
Increased Intra-cranial tension.
Epilepsy
Asthma & chronic obstructive pulmonary disease
Pregnancy & Labor»_space; neonatal asphyxia
Pregnancy & Labor:
use of Papaverine
Smooth muscle e.g. Bronchial, Biliary, GIT, Urinary & Uterus —
Useful in Colic.
therapeutic uses of Meperidine
1- Severe Visceral pain e.g. Myocardial infarction.
2- Alone in Biliary & Renal colic.
3- Pre-anesthetic medication (Better than Morphine).
4- Obstetric Analgesia: Less inhibition of Fetal R.C.
Therapeutic Uses of codiene
Antitussive
Analgesic in Mild & Moderate visceral pain + Aspirin & Paracetamol.
morphine analogue which is Spasmolytic
Papaverine
used in Obstetric Analgesia:
Meperidine
used in Neurolept- Analgesia
Fentanyl + Droperidol
uses of methadone
a- Analgesm in Severe visceral pain e.g. Terminal cancer.
b- To substitute Morphine & Heroin during their withdrawal.
used to substitute Morphine & Heroin during their withdrawal.
Methadone
moa of tramadol
timulate Opiate receptors & decrease Uptake of Noradrenaline & Serotonin.
Treatment of tramadol toxicity:
- Airway, Breathing, Oxygen, Circulation (ABC), Vasopressors
- 5-HT3 antagonists as ondansetron
- Naloxone will only revert some of the symptoms, while increasing the risk of seizures
uses of mixed agonist antagonist analgesics
diagnosis of morhine addiction
2- IF NO Morphine addiction — Kappa (k)-Agonist — Analgesic.
3- IF Morphine Addiction—u-Antagonist — Withdrawal manifestations.
Therapeutic uses of Naltrexone
a- Orally to maintain the Opiate-free state of treated addict.
b- Acute Morphine poisoning.
c-Reduce craving to alcohols and cigarette smoking
Mixed Agonist (k) — Antagonist
Pentazocine, Buprenorphine, Nalbuphine and Butorphanol
combined with olanzapine (atypical antipsychotic) for the treatment of schizophrenia and acute or maintenance of patients with bipolar
Samidorphan (opioid antagonist)
Therapeutic uses of Naloxone
a- Acute Morphine poisoning
b- Opioid-induced Neonatal asphyxia—» Mother (IM) or Neonate (Intraumbilical).
c- Diagnosis of Opioid addiction — S.C. — Withdrawal manifestations e.g. Mydriasis
Mechanism of Action of NSAIDs:
Inhibit COX»_space; decrease synthesis of prostaglandins (PGs), Prostacyclin (PGl2) &Thromboxane-A2
w
dynamics of salicylates
Aspirin produces irreversible inhibition of COX enzymes (1, 2 & 3) by acetylation.
1-C.N.S:
A) Analgesic:
1- Central mechanism»_space; decrease PG»_space; increase Pain threshold especially in Thalamus.
2- Peripheral mechanism»_space; decrease PG»_space; decrease Sensitivity of Nociceptors (Pain receptors) to Histamine, Bradykinin & 5-HT — Anti-inflammatory.
B) Anti-Pyretic:
1- decrease Synthesis of PG induced by IL & Other cytokines — Reset = Readjust Hypothalamic Heat Regulating Center — increase Heat Loss by:
a- Peripheral V.D. - increase Heat loss by radiation.
b- increase Sweating — increase Heat loss by evaporation.
¢- Mobilizes fluids from tissues to plasma.
2- Toxic Dose — Hyperthermia due to Uncoupling of Oxidative-Phosphorylation.
2-Anti-Inflammatory & Anti-Rheumatic:ٌ
ٌٌRespiratory alkalosis
Toxic dose in Children»_space; Metabolic acidosis
May precipitate bronchial asthma
Pain, Ulcer & Bleeding.
Nephropathy
Peripheral acting opioid antagonists
Mechanism of analgesic activity
They block enteric opioid receptors, with limited ability to cross BBB
Members
Methylnaltrexone bromide Naloxegol Alvimopan
Therapeutic uses
Opioid-induced constipation in chronic noncancer pain treatment and late-stage advanced disease
Postoperative ileus following bowel resection
a long-acting potent opioid antagonist
Nalmefene
Non-Selective COX ~ Inhibitors:
Salicylates: Aspirin — Acetylation — Irreversible inhibition of COX enzymes.
Pyrazolones:
Propionic_acid Derivatives: Naproxen, ibuprofen, fenoprofen, flurbiprofen,
Indoles: Indomethacin,
Fenamates:
Phenylacetic Acid Derivatives: Diclofenac.
Oxicams: Piroxicam,
Selective COX-2 Inhibitors (COXIBs)
COXIBs Celecoxib, etoricoxib, parecoxib,
Selective COX-3 inhibitors:
Paracetamol
Systemic Uses of aspirin
1- Anti-pyretic
2- Analgesic
3- Common cold
4- Rheumatic fever (Arthritis)
5- Leukocytosis.
5- Rheumatoid arthritis
6- Chronic gout
7- Antiplatelet
Adverse Effects & Toxicity of Salicylates:
1- Acute Toxicity:
Hyperpyrexia, Hyperventilation & Hyperhidrosis — Dehydration.
Hyperacidity , ulcer , bleeding
acid\base imbalance
4- G.1.T. irritation — Nausea, voting, pain, ulceration & bleeding
9- Nephropathy.
causes reyes syndrome
aspirin
managmenet of toxicity of aspirin
Stomach wash by Sodium bicarbonate.
Alkalization of urine + Forced diuresis
are useful in Aspirin-induced asthma
LOX-inhibitors & Cysteinyl LT-1 receptor blocker
uses of indole derivatives
- closure of patent ductus arteriosus.
- Acute gouty arthritis
Indole derivatives
indomethacin
from NSAID causes corneal opacity
Indomethacin
treatment of closure of patent ductus arteriosus.
Indomethacin
advantage of propionic acid derivatives (profen) on aspirin
less gastric irritation
Dynamics of Paracetamol
1- Inhibit COX-3 in C.N.S.Mainly— Anti-pyretic Analgesic — As potent as Aspirin.
2- Almost No peripheral Action — Almost No Anti-inflammatory & Almost No effect on respiration, C.V.S., Platelet aggregation, Gastric acidity or Uric acid.
managment of toxicity of paracetamol
I.V. N-Acetylcysteine (Rich in S-H) + Oral Methionine.
causes opacities of cornea and lens
phenothiazine: chlorpromazine
