Therapeutic profile of drugs of abuse and other CNS disorders Flashcards
D’soA that may have therapeutic uses (5)
- Cannabis
- Cocaine
- Ketamine
-Amphetamine
-Ecstacy-MDMA
Cannabis- Medical indications: (6)
THC - CB1 (+ CB2r) - class B - harm to users + others
- ↓N/V in chemotherapy patients
- Alleviates chronic pain
- Neurological problems
- ↑appetite in HIV patients
*redu PTSD
6 steps of Emesis / Vomiting (6)
Vomiting centre co-ordinates complex events
1)Vomiting centre – nucleus tractus solitarius (NTS)
NTS, nerve impulses:
- Cranial nerves (upper GI tract)
- Spinal nerves to diaphragm & abdominal muscles
2)Reverse peristalsis
- Begins at ileum → duodenum → stomach
3)Closure of epiglottis over trachea
4)Oesophagus and gastric sphincter relax
5)Abdominal muscles contract
6)Gastric contents ejected
Pathophysiology of Emesis (5)
1) chemo drugs + Chemoreceptor
Trigger Zone (CTZ)
(Outside BBB) - DAr , 5HT3, deltar, CB1, NK1
2) = Medulla - vomiting centre - Muscarinic, 5 HT3 & Histaminic H1, mu r, NK1
3) Pharynx + GIT - w/ chemo + radiotherapy = 2 -5 HT3 receptor
4) Vestibular nuclei + motion sickness = 2 -Muscarinic
Histaminic H1
5) Cerebral cortex +(smell, sight, thought) anticip emesis = 2
Chemotherapy-induced nausea/vomiting (CINV) - cannabis (2)
shown to effective - more effective than conventional anti-emetics - used in US for emesis (nabilone)
however side effects:
- LT use = hyper emesis
- Anxiety
-panic
-psychosis
- hallucinations
-loss of coordination
- ↑HR
Cannabis - Chronic Pain (5)
Benefits > Risk?
Effective? Safe?
some studies say yes (Deshpande et al 2015)
some studies say no (Andreae et al 2015)
used for MS in 10 countries
Neurological Problems - cannabis (4)
used for - MS , epilepsy , Huntington’s chorea
efficacy?
subjective relief
patient-reported relief
=PLACEBO???
Cocaine -Medical indications + side effects (3)
Class A - DA/SERT/NET blockade
Nasal surgery: Vasoconstriction by Blockade of voltage-gated Na+ channels (loss of nasal cavity/septum)
side effects:
Anxiety
panic
↑heart rate
↑BP
depression
Amino Acid Transmitters:
Glutamate - ag + antag (3)
blockade of NMDA r e.g. ion channels (glutamate) - for synp plas, LT potentiation (learning/mem)
NMDA antagonist:
Antiepileptic
Schizophrenia
Loss memory
agonists:
epilepsy
Antipsychotic
antidepressant
Cognitive enhancer
ADHD
Ketamine -Medical indications + side effects: (5)
Class C - NMDA R blockade (mostly)
- Anaesthetic-Children, but not (usually) adults (no hallo in kids)
- Treatment-resistant depression
- Pain
side effects:
Anxiety
panic
psychosis
hallucinations
↑heart rate
↑blood pressure
Ket can be a drug of choice (2)
- Ketamine does not suppress breathing
- Traumatic shock increases risk of hypotension;
ketamine stimulates the circulatory system
Current Pharmacotherapy
of anti-depressants - 3 (3)
1st line = SSRI’s - block sert r - so sert can’t get back into the neurone after being released = major surge in synp cleft
TCA’s = 2nd line: work by blocking SERT + NA transporters = inc of SET + NA in synp cleft
MOAi: 3rd line (not really used) - block the drug blocks enzyme hat breaks down SERT + NA = inc of both
Problems with current antidepressants (4)
*Side effects (especially insomnia=>relapse)
*Toxic with overdose
*Delayed effects
*Non responsive in certain people (30-40% fail to improve with drug treatment)
ket: Treatment-Resistant Depression (4)
- Given at MUCH lower doses than that used to induce analgesia
- Rapid onset (within 2 hours)
- But…cause dissociative symptoms (hallo) , abuse potential
better than electroconvulsive therapy in major depressed hospitalised patients - quicker + better lower rates
Ketamine Bladder - LT use
necrosis in the bladder = bag for their bladder
ket - chronic pain (2)
studies = efficacy for chronic pain
however diff to overcome LT side effects
ket: inhib Pain transmission: Transmitters in the dorsal horn (3)
blocks NMDA r in dorsal horn to prevent transmission from the peripheral to the brain
in chronic pain = hypersensitised pathway from periphery to dorsal horn (even w/o stim. ) = constant triggering of pain pathway = glut release z= contin activation of NMDA - KET BLOCKS THIS
Amphetamines -Medical indications + side effects: (7)
Class B - eventual DAT/SERT/NET reversal = inc monoamines
- ADHD
- Anti-Depressant
- Stroke
- Narcolepsy
- Appetite suppressant
side effects:
Anxiety
panic
paranoia
delusions
↑heart rate, ↑BP
insomnia
ADHD - Amp (3)
- Attention deficit hyperactivity disorder (Ritalin + adderall)
- Abnormal brain structure/function can be resolved upon chronic amphetamine administration (frontal cortex hypoactivity + maladaptations) - symptoms reversed by AMP
- Relatively safe at the dose prescribed
Anti-Depressants - amp
- SSRIs, TCAs, SNRI, MAOIs - reduces SER + NA release like these drugs
Stroke - amp (5)
stroke caused by o2 depravation + haemorrhages
- Amphetamine increases noradrenaline in the synapse
- not to use during stroke - useful in rehab period
- inc/speed up rehab - psychostim = inc reward/motivation etc
- Also used to boost cancer-patient morale
= QUALITY OF LIFE
Amphetamine for narcolepsy (4)
extreme sleepiness - ant any period of time
inc of NA due to AMP = wakefulness
Narcoleptics do not ever get addicted to amphetamines
- Why? Orexin neuropeptide - pro-appetite + arousal: inc of orexin = addictions - in narcolepsy patients = no/low orexin = no addiction story
Ecstasy/MDMA - medical indications + side effects: (4)
Class A - eventual DAT/SERT/NER reversal
- PTSD
- Anti-Depressant
side effects:
Anxiety
panic
paranoia
delusions
↑heart rate
↑BP
Psychotomimetic - MDMA (ecstasy) (5)
- Inhibits monoamine transporters (mainly 5-HT)
- Also releases 5-HT
- Large inc 5-HT (followed by depletion)
- inc 5-HT linked to psychotomimetic effects
- inc DA linked to euphoria (followed by rebound dysphoria)
PTSD - amp (3)
- Post-Traumatic Stress Disorder - hyperactivity of amygdala (emotional region)
- MDMA administered twice (+ 8hr psychotherapy session)
- Improvements still apparent 6 years post treatment
- Mechanism? MDMA - reward + social behaviour (empathy etc.) = due to Incr 5HT, oxytocin
Psilocybin (2)
- derivative of LSD : Magic mushroom psychedelic ingredient could help treat people with severe depression’
Trials of psilocybin blocked by drugs law red tape, says
Professor David Nutt of Imperial College London (LSD ban by Richard Nixon)
SUMMARY (6)
- Are illegal drugs bad?
- Could they be good?
- Dose is important
- Route of administration is important
- Some drugs of abuse may become important therapies
- Some therapies may become abused (benzos, opioids)
