Pharmacology π Flashcards
what are Sedatives & hypnotics? (Minor tranquilizers)
These are centrally acting drugs used mainly to treat anxiety and insomnia.
what is Anxiety?
- is a subjective phenomenon, in which the patient is restless and agitated, has tachycardia, increased sweating and often GIT disorders. It interferes with normal productive activities.
what is Insomnia?
- Includes a wide variety of sleep disturbances such as difficulty in falling asleep, early or frequent awakening and remaining non- refreshed after sleep
Clasiification of Minor Tranquilizers
Sedatives (Anxiolytics):
- Benzodiazepines
- Non-Benzodiazepines: Barbiturates, Buspiron
Hypnotics:
- Benzodiazepines
- Non-Benzodiazepines: Barbiturates, Zaleplon, Ramelteon
Pathophysiology of anxious disorders
Abnormal regulation of neurobiological substrates :
* 5-HT, GABA, Glutamate
* Autonomic nervous system
* Hypothalamo- hypophysis axis
* Neuropeptides: CCK, P substanceβ¦..
Why have Benzodiazepines replaced barbiturates?
Benzodiazepines are the most widely used anxiolytic and hypnotic drugs. They have largely replaced barbiturates since they have:
1) Wide safety margin.
2) Fewer side effects.
3) Less interactions.
4) More tolerance.
Mechanism of action of Benzodiazepines
- They depress the limbic system (Thought and mental function) and reticular activating system (Wakefulness).
- Benzodiazepine receptor stimulation enhance the affinity of GABA to their receptors resulting in hyperpolarisation through Cl-channel opening.
- They produce calming effect and cause anterograde amnesia during the duration of the drug.
- At high dose can produce hypnosis.
Classification of Benzodiazepines
Pharmacological effects of Benzodiazepines
- Anxiolytic
- Sedation & hypnosis
- M. relaxation
- Anticonvulsant
- Amnesia in large dose
Absorbtion of Benzodiazepines
- Well absorption ( Clorazepate is a prodrug ) hydrolysed in the stomach.
Metabolism of Benzodiazepines
- Hepatic metabolism by oxidation into active metabolites of the long acting. By conjugation into inactive metabolites of the short acting.
- Lorazepam and oxazepam are metabolized extrahepatically (utilized in hepatic patients)
Plasma protein binding of Benzodiazepines
10 % pl. pr. Binding.
Uses of Benzodiazepines
Side effects of Benzodiazepines
- Sedation
- Dysarthria
- Paradoxical excitement
- Rebound insomnia
- Tolerance
- Amnesia
- Diplopia
- Hang over
- Dependence
- Apnea
Precautions of Benzodiazepines
1- Driving
2- Pregnancy&Lactation
3- Hepaticencephalopathy
4- + CNS depressants
Contraindications of Benzodiazepines
1- Myasthenia gravis.
2- Severe respiratory impairment e.g sleep apnea
Why are short acting benzodiazepines more of a problem with addiction than the long acting ones?
- Drugs with short half-lives are cleared from the blood stream fairly quickly and may induce withdrawal effects such as rebound excitement and insomnia.
- Those with longer half-lives are cleared less quickly resulting in a decrease in withdrawal effects.
- The resulting slow drop in blood levels allows the body to adjust to the lack of drug more effectively
Withdrawal from Benzodiazepines
- Abrupt cessation: > seizures
- Withdrawal symptoms may occur between doses during continuous use (inter- dose withdrawal). Patients may think these symptoms are due to the original problem.
- Withdrawal symptoms: increased anxiety, sleep disorder, aching limbs, nervousness & nausea.
- Withdrawal experienced by 45% of patients discontinuing low dose benzodiazepines & 100% patients on high doses.
- Short half-life benzodiazepines are associated with more acute & intense withdrawal symptoms.
- Long half-life benzodiazepines - milder, more delayed withdrawal.
Overdose Benzodiazepines
- Generally safe in overdose unless mixed with alcohol/CNS depressants.
- Symptoms of overdose: hypotension, respiratory depression & coma.
- Treatment: Supportive
- Flumazenil rarely indicated
Physical dependence of benzodiazepines
Occurs in about 1 in 3 patients.
what increases risk dependence on benzodiazepines?
History substance abuse
what potentiates the adverse effects of benzodiazepines?
Alcohol & CNS depressants
what is the antidote of Benzodiazepines?
- Flumazenil is the antidote of Benzodiazepines (competitive inhibitor).
- Flumazenil is a benzodiazepine Antagonist = Blocker
- Flumazenil binds to GABA receptor displacing benzodiazepine
when is flumazenil Dangerous to use?
- if mixed overdose (e.g benzodiazepine + tricyclics, amphetamines, other pro-convulsants)
- Result in uncontrolled seizure
what happens when flumazenil is used in dependent individuals?
severe withdrawal symptoms
Dosage of Flumazenil
- Flumazenil has a shorter half life ( one hour) than all benzodiazepines
- Therefore, repeat doses of flumazenil may be required to prevent recurrent symptoms of overdosage once the initial dose of flumazenil wears off.
What is Buspiron?
Anxioselective 5 HT-1A agonist
Half life of Buspiron
has a t1β2 of 7 hr, a long delay (2 or more weeks).
Uses of Buspiron
anti-depression
Side effects of Buspiron
Safer:
- Minimal residual effect,
- No tolerance,
- No rebound insomnia,
- Suitable for elderly
- No withdrawal effect,
- No abuse potential (only in large dose)
- no dependence
What is Zaleplon?
Benzodiazepine-like hypnotic: (not chemically but binds to the same receptor)
Uses of Zaleplon
hypnotic: used for a short term
Side effects of Zaleplon
Safer:
- Minimal residual effect
- No rebound insomnia
- Suitable for elderly
- No hangover
What is Rameteon?
- Selective melatonin agonist (MT1 & MT2)
Uses of Rameteon
hypnotic: for difficulty in falling asleep
Side effects of Rameteon
Induces dizziness and fatigue
What is the drug of choice in cases of:
- Anxiety
- Buspiron, Oxazepam, Alprazepam
What is the drug of choice in cases of:
- Old age anxiety
Buspiron
What is the drug of choice in cases of:
- Insomnia
Lorazepam and oxazepam, Zaleplon
What is the drug of choice in cases of:
- Old age insomnia
Zaleplon, Rameteon
What is the drug of choice in cases of:
- Hepatic patient anxiety or insomnia
Lorazepam and oxazepam
What is the drug of choice in cases of:
- Difficulty in falling asleep
Zaleplon, Rameteon
What is the drug of choice in cases of:
- Preanesthetic medication & Endoscopy
Midazolam, Triazolam
What is the drug of choice in cases of:
- Anesthesia
Diazepam, Thiobarbitone
What is the drug of choice in cases of:
- Anticonvulsant
Diazepam
What is the drug of choice in cases of:
- Antiepileptic
Clonazepam
what is the Ideal anxiolytic drug?
1- Should calm the patient without causing too much day-time sedation and drowsiness and without producing physical or psychological dependence.
2- Has very low toxicity.
3- Should not interact with other medications.
what is the Ideal hypnotic drug?
- Should allow the patient to fall asleep quickly.
- Should maintain sleep of sufficient quality and duration.
- The patient awakes refreshed without a drug hangover.
- Has very low toxicity.
- Should not interact with other medications.
Benzodiazepines key points
- Should not be used in patients with liver disease, history of substance abuse, severe respiratory distress, performing hazardous tasks
- Avoid during pregnancy/lactation if possible
- Assess for over sedation
- Cease slowly
- Monitor elderly (cognition, falls)
- Be aware they raise seizure threshold, and
- Potentiate CNS depressants (alcohol)
Hypnotic key points
- Advise rebound insomnia when medications ceased
- Should not be used in sleep apnoea
- Avoid alcohol
- Hangover effect (impairing performance)
- Monitor in elderly (falls, double dosing)
Classification of analgesics
- Opioid analgesics
- NSAIDs
- Analgesics antipyretics (Acetaminophen)
- For specific painful conditions e.g. ergotamine for migraine
what are Types of Pain?
Severe, Low intensity pain, Itching
what are the main peripheral sense organs that respond to noxious stimuli?
Polymodal nociceptors (PMN)
Example of Visceral pain
myocardial infarction
what is Neuropathic pain?
damage to nerves (trigeminal neuralgia, postherpetic pain, diabetic neuropathy)
Opoid receptors
- Mu (ΞΌ)
- Kappa (Ξ)
- Sigma (Ο)
- Delta (Ξ΄)
Actions of Mu (ΞΌ) receptors
(ΞΌ1): supraspinal analgesia, euphoria
(ΞΌ2): Respiratory depression, conistipation
Actions of Kappa (Ξ)
Spinal analgesia
Actions of Sigma (Ο. receptors
Dysphoria, hallucination, respiratory and vasomotor stimulation
Actions of Delta (Ξ΄) receptors
Modulation of Mu activities
Mechanism of action of opiods
Analgesia:
- By acting presynaptically to inhibit substance P release at the dorsal horn of spinal cord, causing analgesia (k receptors)
- Activation of the descending inhibitory mesospinal tract (ΞΌ)
what do the psychic effect of opiods result from?
- results from diminution of the release of noradrenaline by the neurons of the locus ceruleus
Classification of opioid drugs
- Natural
- Semisynthetic
- Synthetic
what are natural opioids?
what are Semisynthetic opioids?
1-Heroin
2-Hydromorphine
what are synthetic opioids?
Agonists:
1.Meperidines
2-Methadones
3-Tramadole
Agonist-Antagonist:
1-Nalorphine
2-Nalbuphine
3-Pentazocin
4-Butorphanol
5-Bupernorphine
Antagonists:
1-Naloxone
2-Naltrexone
Source of Morphine
- Papaver somniferum, commonly known as the opium poppy
- It is the species of plant from which opium and poppy seeds are derived
Pharmacokinetics of Morphine
Routes of administration:
- Oral: latency to onset (15 β 60 minutes)
- it is also sniffed and injected.
βββ
- t1β2: 4 β 5 hours)
βββ
- First-pass metabolism results in poor availability (25 %) from oral dosing, (glucuronide conjugation)
βββ
- 30% is plasma protein bound
βββ
- 90 % renal elimination & 10 % by hepatic conjugation
receptors of Morphine
AGONIST for mu, kappa, and delta receptors.
Pharmacological effects of Morphine
- CNS effects
- Autonomic effects
- Cardiovascular effects
- Iching
- Spasmogenic effects
CNS effects of Morphine
1- Analgesia (dose dependent), (sensory &emotional)
2- Euphoria
3- Miosis
4- Respiratory c. depression
5- Cough c. suppression
6- Vagal stimulation
7- Nausea and vomiting
Autonomic effects of Morphine
1- Stimulation of Edinger Westphal nucleus producing miosis.
2- Stimulation of vagal nucleus producing hypotension and bronchoconstriction.
CVS effects of Morphine
- Hypotension due to depression of vasomotor center and histamine release.
Iching by Morphine
due to histamine release
Spasmogenic effects by Morphine
1- Spasmodic nonpropulsive contractions of GIT producing conistipation.
2- Of sphincter of Oddi (increasing biliary pressure)
3- Of detrusor muscle tone in the urinary bladder producing a feeling of urinary urgency.
4- Of vesical sphincter tone making voiding difficult
5- Of bronchi due to histamine release and vagal stimulation
Preparations of Morphine
Morphine sulphate and hydrochloride
Adverse effects & Contraindications of Morphine
Treatment of acute Morphine toxicity
- Gastric lavage with pot. Permanganate
- Artificial ventilation by positive pressure if pulmonary edema is present
- Opioid antagonist
Compare between codeine & Morphine in terms of:
- Source
- Pharmacokinetics
- Pharmacodynamics
- Uses
- Sedation & resp. depression
- Addiction
Compare between Morphine, Fentanyls & Meperidine (pethidine) in terms of:
- Source
- Pharmacokinetics
- Pharmacodynamics
- Uses
- S.E
Drugs & Mu and Kappa Receptors
Compare between naltrexone & Naloxone in terms of:
- Potency
- Latency to onset
- Duration of action
- Peak effect
- SE
Compare between opiates & non-opiates in terms of:
- Type of pain
- Site of action
- Addiction
- Analgesia accompanied by
Summary of opiods
