Pharmacology π Flashcards
1
Q
what are Sedatives & hypnotics? (Minor tranquilizers)
A
These are centrally acting drugs used mainly to treat anxiety and insomnia.
2
Q
what is Anxiety?
A
- 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.
3
Q
what is Insomnia?
A
- Includes a wide variety of sleep disturbances such as difficulty in falling asleep, early or frequent awakening and remaining non- refreshed after sleep
4
Q
Clasiification of Minor Tranquilizers
A
Sedatives (Anxiolytics):
- Benzodiazepines
- Non-Benzodiazepines: Barbiturates, Buspiron
Hypnotics:
- Benzodiazepines
- Non-Benzodiazepines: Barbiturates, Zaleplon, Ramelteon
5
Q
Pathophysiology of anxious disorders
A
Abnormal regulation of neurobiological substrates :
* 5-HT, GABA, Glutamate
* Autonomic nervous system
* Hypothalamo- hypophysis axis
* Neuropeptides: CCK, P substanceβ¦..
6
Q
Why have Benzodiazepines replaced barbiturates?
A
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.
7
Q
Mechanism of action of Benzodiazepines
A
- 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.
8
Q
Classification of Benzodiazepines
A
9
Q
Pharmacological effects of Benzodiazepines
A
- Anxiolytic
- Sedation & hypnosis
- M. relaxation
- Anticonvulsant
- Amnesia in large dose
10
Q
Absorbtion of Benzodiazepines
A
- Well absorption ( Clorazepate is a prodrug ) hydrolysed in the stomach.
11
Q
Metabolism of Benzodiazepines
A
- 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)
12
Q
Plasma protein binding of Benzodiazepines
A
10 % pl. pr. Binding.
13
Q
Uses of Benzodiazepines
A
14
Q
Side effects of Benzodiazepines
A
- Sedation
- Dysarthria
- Paradoxical excitement
- Rebound insomnia
- Tolerance
- Amnesia
- Diplopia
- Hang over
- Dependence
- Apnea
15
Q
Precautions of Benzodiazepines
A
1- Driving
2- Pregnancy&Lactation
3- Hepaticencephalopathy
4- + CNS depressants
16
Q
Contraindications of Benzodiazepines
A
1- Myasthenia gravis.
2- Severe respiratory impairment e.g sleep apnea
17
Q
Why are short acting benzodiazepines more of a problem with addiction than the long acting ones?
A
- 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
18
Q
Withdrawal from Benzodiazepines
A
- 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.
19
Q
Overdose Benzodiazepines
A
- Generally safe in overdose unless mixed with alcohol/CNS depressants.
- Symptoms of overdose: hypotension, respiratory depression & coma.
- Treatment: Supportive
- Flumazenil rarely indicated
20
Q
Physical dependence of benzodiazepines
A
Occurs in about 1 in 3 patients.
21
Q
what increases risk dependence on benzodiazepines?
A
History substance abuse
22
Q
what potentiates the adverse effects of benzodiazepines?
A
Alcohol & CNS depressants
23
Q
what is the antidote of Benzodiazepines?
A
- Flumazenil is the antidote of Benzodiazepines (competitive inhibitor).
- Flumazenil is a benzodiazepine Antagonist = Blocker
- Flumazenil binds to GABA receptor displacing benzodiazepine
24
Q
when is flumazenil Dangerous to use?
A
- if mixed overdose (e.g benzodiazepine + tricyclics, amphetamines, other pro-convulsants)
- Result in uncontrolled seizure
25
what happens when flumazenil is used in dependent individuals?
severe withdrawal symptoms
26
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.
27
What is Buspiron?
Anxioselective 5 HT-1A agonist
28
Half life of Buspiron
has a t1β2 of 7 hr, a long delay (2 or more weeks).
29
Uses of Buspiron
anti-depression
30
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
31
What is Zaleplon?
Benzodiazepine-like hypnotic: (not chemically but binds to the same receptor)
32
Uses of Zaleplon
hypnotic: used for a short term
33
Side effects of Zaleplon
Safer:
- Minimal residual effect
- No rebound insomnia
- Suitable for elderly
- No hangover
34
What is Rameteon?
- Selective melatonin agonist (MT1 & MT2)
35
Uses of Rameteon
hypnotic: for difficulty in falling asleep
36
Side effects of Rameteon
Induces dizziness and fatigue
37
What is the drug of choice in cases of:
- Anxiety
- Buspiron, Oxazepam, Alprazepam
38
What is the drug of choice in cases of:
- Old age anxiety
Buspiron
39
What is the drug of choice in cases of:
- Insomnia
Lorazepam and oxazepam, Zaleplon
40
What is the drug of choice in cases of:
- Old age insomnia
Zaleplon, Rameteon
41
What is the drug of choice in cases of:
- Hepatic patient anxiety or insomnia
Lorazepam and oxazepam
42
What is the drug of choice in cases of:
- Difficulty in falling asleep
Zaleplon, Rameteon
43
What is the drug of choice in cases of:
- Preanesthetic medication & Endoscopy
Midazolam, Triazolam
44
What is the drug of choice in cases of:
- Anesthesia
Diazepam, Thiobarbitone
45
What is the drug of choice in cases of:
- Anticonvulsant
Diazepam
46
What is the drug of choice in cases of:
- Antiepileptic
Clonazepam
47
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.
48
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.
49
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)
50
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)
51
Classification of analgesics
- Opioid analgesics
- NSAIDs
- Analgesics antipyretics (Acetaminophen)
- For specific painful conditions e.g. ergotamine for migraine
52
what are Types of Pain?
Severe, Low intensity pain, Itching
53
what are the main peripheral sense organs that respond to noxious stimuli?
Polymodal nociceptors (PMN)
54
Example of Visceral pain
myocardial infarction
55
what is Neuropathic pain?
damage to nerves (trigeminal neuralgia, postherpetic pain, diabetic neuropathy)
56
Opoid receptors
- Mu (ΞΌ)
- Kappa (Ξ)
- Sigma (Ο)
- Delta (Ξ΄)
57
Actions of Mu (ΞΌ) receptors
(ΞΌ1): supraspinal analgesia, euphoria
(ΞΌ2): Respiratory depression, conistipation
58
Actions of Kappa (Ξ)
Spinal analgesia
59
Actions of Sigma (Ο. receptors
Dysphoria, hallucination, respiratory and vasomotor stimulation
60
Actions of Delta (Ξ΄) receptors
Modulation of Mu activities
61
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)
62
what do the psychic effect of opiods result from?
- results from diminution of the release of noradrenaline by the neurons of the locus ceruleus
63
Classification of opioid drugs
- Natural
- Semisynthetic
- Synthetic
64
what are natural opioids?
65
what are Semisynthetic opioids?
1-Heroin
2-Hydromorphine
66
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
67
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
68
Pharmacokinetics of **Morphine**
**Routes of administration:**
- Oral: latency to onset (15 β 60 minutes)
- it is also sniffed and injected.
**---------**
- t1β2: 4 β 5 hours)
**---------**
- First-pass metabolism results in poor availability (25 %) from oral dosing, (glucuronide conjugation)
**---------**
- 30% is plasma protein bound
**---------**
- 90 % renal elimination & 10 % by hepatic conjugation
69
receptors of **Morphine**
AGONIST for mu, kappa, and delta receptors.
70
Pharmacological effects of **Morphine**
- CNS effects
- Autonomic effects
- Cardiovascular effects
- Iching
- Spasmogenic effects
71
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
72
Autonomic effects of **Morphine**
1- Stimulation of Edinger Westphal nucleus producing miosis.
2- Stimulation of vagal nucleus producing hypotension and bronchoconstriction.
73
CVS effects of **Morphine**
- Hypotension due to depression of vasomotor center and histamine release.
74
Iching by **Morphine**
due to histamine release
75
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
76
Preparations of **Morphine**
Morphine sulphate and hydrochloride
77
Dosage of **Morphine**
- S.C., I.M, I.V. and epidural
- 10 mg S.C. or I.M. for adult, 5mg I.V.
- 0.1-0.2 mg/day SC or IM for infants and children.
- The dose frequency / 4-5 hours
- Sustained release oral preparation 1-2 mg /12 hours & transdermal patches.
78
Adverse effects & Contraindications of **Morphine**
79
Uses of **Morphine**
- Analgesia of moderate to severe pain
- Acute pulmonary edema
- In anesthesia
- Colic : + atropine
80
Why is **Morphine** used in Acute pulmonary edema?
- peripheral VD
- relieve of anxiety
- decrease of tachypnea
81
How is **Morphine** used in anethesia?
- as preanaethetic medication
- as adjuvant to anesthetic agents (iv morphine)
- as regional anesthesia; epidural injection of morphine. It produces long lasting analgesia with minimal side effects.
82
Symotoms and signs of acute toxicity of **Morphine**
- coma with depressed respiration, pin point pupils, hypotension , pulmonary edema and shock may occur.
83
Treatment of acute **Morphine** toxicity
- Gastric lavage with pot. Permanganate
- Artificial ventilation by positive pressure if pulmonary edema is present
- Opioid antagonist
84
Symptoms and signs of Chronic toxicity of morphine (addiction)
- The patient is emaciated, conistipated with frequent flushes and itching.
- The intellectual functions are also depressed.
- Withdrawal results in what is called abstinence S.
85
Opioid withdrawal - abstinence syndrome
Severity depends on dose used and rate of elimination:
- Rhinorrhea
- Lacrimation
- Chills
- Goose flesh
- Muscle aches
- Diarrhea
- Yawning
- Anxiety
- Hyperalgesia
(Precipitated withdrawal by a partial agonist or antagonist administration)
86
What is drug addiction?
- Prolonged use of prescribed medications for pain, anxiety produce tolerance and physical dependence.
87
What are examples of Commonly Abused Prescription Opiates?
Buprenorphine, Codeine, Fentanyl, Hydrocodone, Hydromorphone,Meperidine, Methadone, Morphine, Oxycodone, Propoxyphene
88
Compare between codeine & Morphine in terms of:
- Source
- Pharmacokinetics
- Pharmacodynamics
- Uses
- Sedation & resp. depression
- Addiction
89
what are examples of Semisynthetic opioid?
1- Heroin (diacetyl morphine)
2- Hydromorphine
90
Characters of Hydromorphine
- More rapid onset & shorter duration
- High risk of respiratory depression & addiction
91
what are synthetic agonist opiods?
**Agonists:**
1.Meperidines
2-Methadones
3-Tramadole
**Agonist-Antagonist:**
1-Nalorphine
2-Nalbuphine
3-Pentazocin
4-Butorphanol
5-Bupernorphine
**Antagonists:**
1-Naloxone
2-Naltrexone
92
what are examples of Meperidines?
- Meperidne (Pethedine)
- Diphenoxylate
- Fentanyl and alfentail
93
Compare between Morphine, Fentanyls & Meperidine (pethidine) in terms of:
- Source
- Pharmacokinetics
- Pharmacodynamics
- Uses
- S.E
94
what are Methadones?
1- Methadone
2- Propoxyphene
95
Route of adminstration of Methadones
Oral
96
Half life of Methadones, and what does it result in?
- Longer t1/2 (24h)
- Can result in cumulative toxicity
97
Metabolism of Methadones
- Metabolized extensively in the liver
98
Uses of Methadones
- Used as analgesic & in the suppression of withdrawal S. Of opiates.
99
Side effects of Methadones
Like morphine
100
Propoxyphene
- codeine as analgesic & as addict
- 1/3 depression of respiration as codeine
- Antitussive
101
what is Tramadole?
- A metabolite of the antidepressant trazodone
102
Pharmacodynamics of Tramadole
Weak agonist at ΞΌ- opioid receptor + weak inhibitor of noradrenaline reuptake
103
Uses of Tramadole
- Widely used as an analgesic for postoperative pain
104
Side effects of Tramadole
- Better side-effect profile than most opioids
105
Does Tramadole depress the RC?
- Does not depress the respiratory C.
106
Is Tramadole addictive?
- Addictive
107
Does Tramadole induce seizures?
- Induce seizures in epileptics
108
Characters of Nalorphine
- analgesic
- less resp. depression
- withdrawal S. in addict
109
Characters of Nalbuphine
- analgesic
- less resp. depression
- withdrawal S. in addict
110
Characters of Pentazocine
- analgesic
- less respiratory C. depression
- does not cause withdrawal S. in addict.
- I.V. elevates systemic & pulmonary artery pressure (so contraindicated in coronary ischemia)
111
Characters of Butorphanol
- analgesic
- less respiratory C. depression
- elevates pulmonary artery pressure (so contraindicated in coronary ischemia)
- does not cause withdrawal S. in addict
112
Characters of Bupernorphine
- analgesic
- respiratory C. depression as morphine
- not antagonised by naloxone
113
Drugs & Mu and Kappa Receptors
114
what are opioid antagonists?
1-Naloxone
2-Naltrexone
115
Compare between naltrexone & Naloxone in terms of:
- Potency
- Latency to onset
- Duration of action
- Peak effect
- SE
116
Compare between opiates & non-opiates in terms of:
- Type of pain
- Site of action
- Addiction
- Analgesia accompanied by
117
Summary of opiods
118
Classification of epilepsies
119
Types of partial (Focal) epilepsies
120
DOC in cases of partial (Focal) epilepsies
121
Types of generalized epilepsies
122
Manifestations of Tonic-clonic (Grand-mal) epilepsy
123
DOC in Tonic-clonic (Grand-mal) epilepsy
124
Manifestations of Absence (Petit-Mal) Epilepsy
125
DOC in cases of Absence (Petit-Mal) Epilepsy
126
Manifestations in myoclonic epilepsy
127
DOC in cases of myoclonic epilepsy
128
Manifestations of Atonic epilepsy
129
DOC in cases of Atonic epilepsy
130
Definition of epilepsy
131
Definition of seizures
132
Clinical presentation of epilepsy
133
EEG of epilepsy
134
what causes failure of therapy of anti-epileptic drugs?
135
Precautions while using anti-epileptic drugs
136
what are types of antiepeleptic drugs (AED)?
137
MOA ofDiphenylhydantoin (Phenytoin)
138
Effects of Diphenylhydantoin (Phenytoin)
139
Uses of Diphenylhydantoin (Phenytoin)
140
what is fosphenytoin?
141
SE of Diphenylhydantoin (Phenytoin)
142
MOA of Carbamazepine (Tegretol)
143
Effect of Carbamazepine (Tegretol)
144
Uses of Carbamazepine (Tegretol)
145
what is oxcarbazepine?
146
SE of Carbamazepine (Tegretol)
147
when is Carbamazepine (Tegretol) contraindicated?
148
MOA of Valproic acid (Depakene)
149
Effects of Valproic acid (Depakene)
150
Uses of Valproic acid (Depakene)
151
SE of Valproic acid (Depakene)
152
MOA of Ethosuximide (Zarontin)
153
Uses of Ethosuximide (Zarontin)
154
AE of Ethosuximide (Zarontin)
155
MOA of Benzodiazepines (Bzds)
156
When are Benzodiazepines (Bzds) indicated in epilepsy?
157
Notes about valproic acid
158
Example of Barbiturates
159
MOA of Barbiturates
160
Uses of Barbiturates
161
when are Barbiturates contraindicated?
162
what are newer AEDs?
163
MOA of Felbamate
164
Uses of Felbamate
165
AE of Felbamate
166
MOA of Lamotrigine
167
Uses of Lamotrigine
168
AE of Lamotrigine
169
MOA of Gabapentin & pregabalin
170
Uses of Gabapentin & pregabalin
171
AE of Gabapentin & pregabalin
172
MOA of Tiagabine
173
MOA of Levetiracetam
174
Uses of Levetiracetam
175
AE of Levetiracetam
176
Advantages of Levetiracetam
177
MOA of Topiramate
178
Why isn't Vigabatrine used anymore?
179
Guidelines for AED
180
what is Status Epilepticus?
181
Treatment of Status Epilepticus
182
why shoudn't phenytoin be given IM?
183
Precautions during antiepileptic therapy
184
First line in trearment of focal epilepsy
185
First line in trearment of generalized epilepsy
186
First line in trearment of absence epilepsy
187
Chances of teratogenecity by AEDs
188
Precautions during taking AEDs during pregnancy
189
What is the best AED during pregnancy?
190
Is Breast feeding acceptable with nearly All anti-epileptic drugs?
